Umbilical Cord Blood Mononuclear Cell Therapy for Patellofemoral Osteoarthritis: A Clinical Investigation

Umbilical Cord Blood Mononuclear Cell Therapy for Patellofemoral Osteoarthritis: A Clinical Investigation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Umbilical Cord Blood Mononuclear Cell Therapy for Patellofemoral Osteoarthritis: A Clinical Investigation Shuwei Jia, Qi Xu, Xian Li, Hongpeng Yang, Shaoda Ren, Da Song, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7836364/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Exploring the Clinical Efficacy and Mechanisms of Action of Intra-Articular Umbilical Cord Blood-Derived Mononuclear Cell (UCB-MNC) Injection in Patellofemoral Osteoarthritis (PFOA) Methods A total of 60 patients with knee osteoarthritis were randomly assigned to either the experimental group (receiving UCB-MNCs injection) or the control group (receiving sodium hyaluronate injection). Follow-up assessments were conducted at 1, 3, 6, and 12 months after the initial treatment. Efficacy indicators, including the Visual Analog Scale (VAS) for pain, the patellofemoral Kujala score, cytokine expression in synovial fluid, and the Whole-Organ Magnetic Resonance Imaging Score (WORMS), as well as safety indicators, were evaluated. Statistical analysis was performed using SPSS 25.0. Results A total of 56 patients were ultimately included, with 51 completing the full follow-up. Baseline characteristics showed no statistically significant differences between the two groups before treatment. After treatment, the experimental group demonstrated superior analgesic effects compared to the control group at 3, 6, and 12 months. The Kujala scores improved gradually in the experimental group, while scores in the control group began to decline after 3 months. Significant reductions in the expression of IL-1β, IL-6, and IFN-γ in synovial fluid were observed in the experimental group, with statistically significant differences compared to the control group. At 6 months post-treatment, the WORMS bone marrow edema score decreased markedly in the experimental group, also showing a statistically significant difference from the control group. The overall clinical effectiveness rate was higher in the experimental group than in the control group at 3, 6, and 12 months after treatment. Adverse reactions in both groups were mild and self-limiting throughout the study. Conclusions Intra-articular injection of UCB-MNCs demonstrates high clinical efficacy and sustained therapeutic effects in the treatment of PFOA, effectively alleviating pain symptoms, improving knee joint function, reducing the expression of inflammatory factors in synovial fluid, and mitigating bone marrow edema. However, further investigation is warranted to validate long-term efficacy and safety due to the current limitations in sample size and duration of follow-up. Knee Osteoarthritis Patellofemoral Osteoarthritis Biological Therapy Umbilical cord blood mononuclear cells Figures Figure 1 Figure 2 Figure 3 Introduction Knee osteoarthritis (KOA) is the most common degenerative disorder of the musculoskeletal system among middle-aged and elderly individuals. Based on the affected compartment, KOA can be classified into three subtypes: isolated tibiofemoral osteoarthritis, isolated patellofemoral osteoarthritis (PFOA), and the mixed type. PFOA is a knee disorder characterized by degenerative changes in the articular surfaces of the patella and the femoral trochlea. It primarily manifests as anterior knee pain, limited mobility, and functional impairment, significantly affecting patients' quality of life[ 1 ]. Current research on KOA, both domestically and internationally, has predominantly focused on tibiofemoral osteoarthritis, while studies specifically targeting PFOA remain relatively limited[ 2 ]. However, PFOA demonstrates a high prevalence among the elderly in community settings, and its incidence is steadily increasing due to the aging population. Studies indicate that the prevalence of PFOA among adults aged 50 and above in China reaches as high as 23.9%, with rates of 20.5% in men and 25.8% in women, making it a major contributor to disability in middle-aged and older adults[ 3 ]. Given its distinct clinical manifestations and pathological features, along with growing research into its epidemiology, risk factors, diagnosis, and treatment, PFOA has attracted increasing attention and interest from researchers worldwide. Currently, clinical management strategies primarily include the use of nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, intra-articular injections (such as corticosteroids or hyaluronic acid), and surgical interventions. However, these approaches are largely limited to symptomatic relief and are unable to reverse cartilage degeneration or promote tissue regeneration. Moreover, long-term application may be associated with risks such as gastrointestinal injury and accelerated cartilage degradation[ 4 ]. Therefore, exploring a biological therapy that combines both reparative and anti-inflammatory effects has become an urgent and critical challenge in the field of osteoarthritis treatment. In recent years, UCB-MNCs have attracted significant attention in the field of regenerative medicine due to their unique biological properties. UCB-MNCs are a heterogeneous population isolated from umbilical cord blood, comprising hematopoietic stem cells, MSCs, endothelial progenitor cells, and immunomodulatory cells [ 5 ]. They exhibit low immunogenicity, multi-lineage differentiation potential, and paracrine activities. Studies have demonstrated that UCB-MNCs facilitate tissue repair through multiple mechanisms: the cytokines they secrete (such as IL-10 and TGF-β) can suppress inflammatory responses and modulate the local immune microenvironment[ 6 ]; meanwhile, the mesenchymal stem cell component can either differentiate into chondrocytes or activate endogenous repair programs via paracrine signaling, thereby promoting cartilage matrix synthesis and angiogenesis[ 7 ]. One clinical study reported that intra-articular injection of UCB-MNCs significantly alleviated pain and improved joint function in patients with knee osteoarthritis, with MRI evidence of partial cartilage repair and therapeutic effects lasting up to six months[ 8 , 9 ]. Furthermore, the successful application of UCB-MNCs in conditions such as Parkinson’s disease, myocardial repair, and ulcerative colitis underscores their potential for cross-tissue regeneration. Although UCB-MNCs have shown promise in the treatment of KOA, their clinical application in PFOA remains exploratory. Current research predominantly focuses on generalized knee degeneration, whereas the patellofemoral joint—due to its distinct biomechanics and anatomical features—may exhibit unique pathological mechanisms and treatment responses compared to other KOA subtypes. Furthermore, critical parameters such as the optimal injection dose, frequency, and long-term safety of UCB-MNC therapy still require systematic evaluation. For instance, Cartistem®, a product developed by Medipost Corp. in South Korea based on umbilical cord blood-derived mesenchymal stem cells, relies on the invasive microfracture procedure, which may increase the risk of complications. In contrast, intra-articular injection of UCB-MNCs alone offers a less invasive alternative with potential clinical advantages[ 10 ]. Based on this background, the present study aims to investigate the clinical efficacy and mechanisms of intra-articular injection of UCB-MNCs in the treatment of PFOA, with a specific focus on its effects on cartilage repair, inflammation modulation, and functional improvement. By integrating imaging outcomes, molecular biological analyses, and patient-reported outcome measures, this research seeks to provide novel strategies for the precision treatment of PFOA and to promote the diversified application of umbilical cord blood-derived resources in regenerative medicine. Materials and methods A total of 60 patients with knee osteoarthritis were recruited from the outpatient department of joint surgery at our hospital, meeting the following inclusion criteria: 1. Aged 30–70 years, either sex. 2.compliance with the diagnostic criteria for patellofemoral osteoarthritis as outlined in the Chinese Guidelines for Patellofemoral Joint Disorders (2020 Edition). 3. MRI-based disease severity classified as grade I to III. 4. Adequate comprehension of the clinical trial protocol and provision of written informed consent by the participant and/or legal surrogate.. Exclusion criteria included known or suspected allergy or severe adverse reactions to the cell-based investigational product or general hypersensitivity; severe patellofemoral osteoarthritis evidenced by MRI grade IV, patellofemoral subluxation, or habitual patellar dislocation; intra-articular injection in the target knee within the past six months or corticosteroid treatment within three months or long-term use of immunosuppressive or anticoagulant medications; non-degenerative arthritic conditions such as tuberculous, neoplastic, rheumatoid, gouty, or ankylosing spondylitis-related knee involvement; infectious arthritis or dermatological manifestations like eczema around the knee; hematologic disorders such as coagulopathies; presence of malignant tumors; severe cardiac or pulmonary dysfunction or poorly controlled diabetes or other conditions considered ineligible by investigators; active infections including HBV, HCV, or HIV; poor compliance or psychiatric illness; participation in other clinical trials within the past month; lactation, pregnancy, or women of childbearing age planning pregnancy; and other circumstances deemed inappropriate for enrollment by researchers. Withdrawal and discontinuation criteria are as follows: 1. Occurrence of a serious adverse event (e.g., anaphylactic reaction) during the trial. 2. Participant-requested withdrawal. 3. Inability to complete follow-up for any reason. 4. Poor compliance or receipt of any concomitant therapy that may influence outcome assessment during the study period.. Based on an a priori sample size estimation conducted using G*Power software, the required sample size for this study was determined. The analysis was configured with a significance level (α) of 0.05 and a statistical power (1 – β) of 0.95 for a one-tailed test. The independent two-sample t-test was selected as the statistical method. Referring to previous experience and relevant domestic and international literature, and accounting for anticipated participant dropout, the number of eligible outpatients available at the study site, practical treatment and follow-up conditions, as well as statistical requirements, a medium-to-large effect size (d = 0.72) was specified. The calculation yielded a total sample size of 50 participants. The cells used in this study were provided by the Shandong Umbilical Cord Blood Bank. Prior to use, all cells underwent comprehensive analysis following separation, purification, and packaging processes to characterize their biological properties, assess viability, and confirm the absence of contamination, thereby ensuring clinical safety for therapeutic application. This study was conducted in accordance with the World Medical Association Declaration of Helsinki and approved by the Ethical Committee of Liaocheng People's Hospital. Informed consent was obtained from the patient who participated in this study. All methods were carried out in accordance with relevant guidelines. The mean age of the patients on whom the models were based was 47.31 ± 6.25 years (range 32–65 years). Participants were sequentially enrolled and randomized into two groups based on their outpatient visit time, with 30 subjects in each group. The experimental group received intra-articular injections of UCB-MNCs at a dose of 2×10⁸ cells in 3 ml normal saline, administered twice with a 3-week interval, while the control group received intra-articular injections of 2 ml sodium hyaluronate (Shupaite®) once per week for a total of five weeks. All injections were performed under standardized aseptic conditions with the patient in a supine position and the knee extended, using the superolateral approach as the puncture site. After routine disinfection and draping, synovial fluid was aspirated and saved for analysis following joint cavity entry confirmed by loss of resistance; repeated aspiration ensured no residual fluid remained before injection. Post-injection, the needle was removed, the site was compressed and dressed, and patients were instructed to perform immediate knee movements to distribute the agent. Post-procedure care included 24 hours of non-weight-bearing activity, resuming general activities thereafter, keeping the site dry for 2 days to prevent infection, and avoiding strenuous exercise for 2 weeks. In cases of post-injection knee swelling and pain, initial management consisted of local ice application and topical flurbiprofen gel patches. For more severe pain, oral NSAIDs, such as celecoxib capsules, were added to alleviate pain and reduce swelling. If unusually significant swelling occurred, patients were advised to return to the hospital for joint aspiration followed by irrigation with normal saline. Follow-ups were conducted at 1, 3, 6, and 12 months after the initial injection. The assessments included both efficacy and safety endpoints. The efficacy observation endpoints included: (a) the VAS for pain assessment; (b) the Kujala score for patellofemoral joint function evaluation, as recommended by the National Clinical Research Center for Geriatric Diseases; (c) analysis of synovial fluid: joint aspiration was routinely performed before injection, and levels of active cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and matrix metalloproteinase-13 (MMP-13), as well as glucose, albumin, and white blood cell count, were measured using enzyme-linked immunosorbent assay (ELISA) before the first injection and three weeks post-injection; (d) evaluation of cartilage degeneration and damage via knee magnetic resonance imaging (MRI), primarily using the WORMS to assess patellar cartilage morphology and bone marrow edema—where cartilage morphology was graded from 0 to 6 (Table 1 )and bone marrow edema was scored from 0 to 3 (Table 2 ); and (e) clinical efficacy assessment using a self-designed evaluation form completed by patients at 1, 3, 6, and 12 months post-treatment, categorizing outcomes as either effective or ineffective. Safety indicators involved documentation of all self-reported adverse events throughout the study period, including their duration, severity, measures taken, outcomes, impact on the primary condition, relationship to the investigational product, and overall assessment. Table 1 Cartilage Morphology Grading Criteria Based on the Whole-Organ Magnetic Resonance Imaging Score (WORMS) System WORMS Score Description 0 Normal cartilage morphology and thickness. 1 Normal cartilage thickness with focal hyperintensity on T2-weighted images. 2 Partial-thickness cartilage defect < 1 cm in width. 2.5 Full-thickness cartilage defect 1 cm in width but involving 75% of the region) partial-thickness cartilage loss. 5 Multiple areas of full-thickness cartilage loss, or a full-thickness defect > 1 cm in width but involving 75% of the region) full-thickness cartilage loss. Table 2 Bone Marrow Edema Scoring Criteria Based on the Whole-Organ Magnetic Resonance Imaging Score (WORMS) WORMS Score Definition 0 No bone marrow edema signal is present in the subchondral bone. 1 Edema involves up to and including 25% of the subchondral bone area. 2 Edema involves between 25% and 50% of the subchondral bone area. 3 Edema involves 50% or more of the subchondral bone area. Statistical analysis was performed using SPSS version 25.0. Measurement data are presented as mean ± standard deviation (mean ± SD). Normality and homogeneity of variance were assessed for all datasets. Baseline characteristics between the experimental and control groups were compared using independent samples t-tests or Mann-Whitney U tests for continuous variables and chi-square tests for categorical variables. Post-treatment comparisons between the two groups for continuous outcomes were analyzed using independent samples t-tests or Mann-Whitney U tests, as appropriate. Within-group comparisons of efficacy outcomes before and after treatment were conducted using paired samples t-tests or Wilcoxon signed-rank tests. A two-tailed p-value of less than 0.05 was considered statistically significant. Results A total of 60 subjects were initially recruited for the study. Following the application of inclusion and exclusion criteria, 56 participants were enrolled, with 28 assigned to each group. Over the one-year follow-up period, 51 patients completed the entire study protocol. Attrition accounted for three patients, with one loss to follow-up in the experimental group and two in the control group. Additionally, two participants were excluded during the trial—one from the experimental group due to a traumatic meniscal tear requiring arthroscopic surgery, and one from the control group due to receiving other treatments for insufficient therapeutic effect, which could potentially confound the outcome assessment. Consequently, data from 51 patients were available for final analysis, including 26 in the experimental group and 25 in the control group. This sample size met the pre-trial estimated minimum requirement of 50 subjects. No significant differences were observed in the baseline characteristics, including gender, age, body mass index (BMI), duration of disease, and Kellgren-Lawrence (K-L) grade, between the two groups among the 51 patients who completed the study (all p > 0.05; Table 3 ). Table 3 Comparison of Baseline Characteristics Between the Two Groups Characteristic Experimental Group (n = 26) Control Group (n = 25) Statistical Value *p*-Value Gender, Male/Female 10 / 16 10 / 15 χ² = 0.013 0.91 Age, years 48.53 ± 7.65 46.04 ± 4.15 *t* = 1.44 0.16 BMI, kg/m² 25.47 ± 1.74 24.84 ± 0.98 *t* = 1.57 0.12 MRI Grade, Ⅰ/Ⅱ/Ⅲ 5 / 6 / 15 5 / 8 / 12 χ² = 0.60 0.74 MRI Grade, Ⅰ/Ⅱ/Ⅲ 26.78 ± 4.29 24.40 ± 4.37 *t* = 1.96 0.06 No significant difference was observed in the VAS scores between the two groups before treatment (P > 0.05), indicating comparable baseline characteristics. At the 1-month follow-up, both groups showed a reduction in VAS scores compared to their respective baseline levels, with no statistically significant difference between the groups (P > 0.05), demonstrating that both interventions were effective in alleviating pain symptoms in patients with patellofemoral osteoarthritis. However, at the subsequent follow-up time points (3, 6, and 12 months), the experimental group exhibited significantly greater pain reduction compared to the control group, and these differences were statistically significant (P < 0.01), suggesting a superior and sustained analgesic effect of the experimental treatment over the conventional approach (Table 4 ). Table 4 Comparison of VAS Scores Between the Two Groups at Different Time Points After Treatment Time Point Group VAS Score (Mean ± SD) *t*-value *p*-value Before Treatment Experimental 5.00 ± 0.94 -1.67 0.10 Control 5.52 ± 1.26 1 Month Experimental 3.08 ± 1.23 -0.94 0.35 Control 3.40 ± 1.22 3 Months Experimental 2.73 ± 1.15 -4.69 < 0.01 Control 4.60 ± 1.66 6 Months Experimental 2.46 ± 1.03 -6.90 < 0.01 Control 5.00 ± 1.55 12 Months Experimental 2.46 ± 1.07 -7.14 < 0.01 Control 5.04 ± 1.49 Prior to treatment, the Kujala scores were 67.58 ± 6.68 in the experimental group and 66.84 ± 7.48 in the control group, with no statistically significant difference between the two groups (t = 0.33; p = 0.71). After treatment, follow-up assessments at 1, 3, 6, and 12 months revealed that the Kujala scores in the experimental group gradually improved (75.85 ± 6.72; 77.15 ± 6.36; 78.19 ± 6.30; 78.27 ± 6.28), indicating that UCB-MNCs injection progressively alleviated knee pain symptoms and enhanced joint function in patients with patellofemoral arthritis. In contrast, the hyaluronic acid treatment group showed an initial increase in the Kujala score at 1 month post-treatment (76.20 ± 7.00), but the scores gradually decreased thereafter (70.92 ± 8.16; 70.28 ± 7.36; 69.08 ± 7.49), suggesting that while hyaluronic acid treatment provided short-term symptomatic relief, its long-term efficacy was limited. (Table 5 ) Table 5 Comparison of Kujala Scores at 1, 3, 6, and 12 Months After Different Treatments Time Point Group Kujala Score (Mean ± SD) t-value p-value Before Treatment Experimental 67.58 ± 6.68 0.37 0.71 Control 66.84 ± 7.48 1 Month Experimental 75.85 ± 6.72 -0.19 0.85 Control 76.20 ± 6.97 3 Months Experimental 77.15 ± 6.36 3.03 < 0.01 Control 70.92 ± 8.16 6 Months Experimental 78.19 ± 6.30 4.13 < 0.001 Control 70.28 ± 7.36 12 Months Experimental 78.27 ± 6.28 4.75 0.05), indicating comparable baseline levels between the experimental and control groups. Since the distribution of pre- and post-treatment differences in IL-1β, IL-6, TNF-α, and IFN-γ was not normal, the Wilcoxon signed-rank test was applied, and interquartile range was used to describe changes in cytokine levels. In the experimental group, IL-1β, IL-6, and IFN-γ levels decreased significantly after treatment (P 0.05). In contrast, the control group showed no statistically significant changes in any of the cytokines (IL-1β, IL-6, TNF-α, or IFN-γ; P > 0.05). After treatment, differences between the experimental and control groups were statistically significant for IL-1β, IL-6, and IFN-γ (P < 0.01), but not for TNF-α. (Table 6 ) Table 6 Comparison of Kujala scores at different time points after treatment between the two groups Time point Group Kujala score (mean ± SD) t-value p-value Before treatment Experimental 67.58 ± 6.68 0.37 0.71 Control 66.84 ± 7.48 1 month Experimental 75.85 ± 6.72 -0.19 0.85 Control 76.20 ± 6.97 3 months Experimental 77.15 ± 6.36 3.03 < 0.01 Control 70.92 ± 8.16 6 months Experimental 78.19 ± 6.30 4.13 < 0.001 Control 70.28 ± 7.36 12 months Experimental 78.27 ± 6.28 4.75 0.05), confirming that the trial and control groups were comparable before intervention. Because the pre–post-treatment differences in all four cytokines deviated from a normal distribution, within-group changes were evaluated with the Wilcoxon signed-rank test and summarised with median and inter-quartile range. After therapy, IL-1β, IL-6 and IFN-γ concentrations in the trial group fell markedly, and the pre- versus post-treatment differences were statistically significant (P 0.05). As illustrated in Fig. 1 , the trial group exhibited pronounced reductions in IL-1β, IL-6 and IFN-γ, whereas levels in the control group remained essentially unchanged or marginally increased. Although TNF-α moved in opposite directions in the two groups, the magnitude of change was small. Consequently, no significant pre–post variations in IL-1β, IL-6, TNF-α or IFN-γ were detected in the control group (P > 0.05). Between-group comparison after treatment demonstrated significantly lower IL-1β, IL-6 and IFN-γ concentrations in the trial group than in controls (P < 0.01), whereas the inter-group difference in TNF-α was not significant.(Table 7 ). Table 7 Comparison of changes in cytokine levels after different treatments Comparison Cytokine Group Level (Median, IQR) Statistical Significance Baseline Comparison IL-1β Experimental 9.98 (7.96, 15.04) p = 0.94 Control 10.63 (8.07, 12.73) IL-6 Experimental 65.09 (32.07, 93.03) p = 0.73 Control 65.86 (27.76, 82.41) TNF-α Experimental 11.76 (6.93, 18.99) p = 0.07 Control 8.31 (5.05, 15.06) IFN-γ Experimental 21.28 (13.39, 27.91) p = 0.64 Control 17.63 (9.57, 49.29) Within-group Changes Experimental Group IL-1β Pre-treatment p < 0.001 Post-treatment 5.93 (4.62, 8.98) IL-6 Pre-treatment p < 0.001 Post-treatment 42.11 (19.49, 60.49) TNF-α Pre-treatment p = 0.17 Post-treatment 10.21 (6.76, 15.91) IFN-γ Pre-treatment p < 0.001 Post-treatment 12.05 (7.89, 17.77) Control Group IL-1β Pre-treatment p = 0.46 Post-treatment 11.86 (8.56, 14.84) IL-6 Pre-treatment p = 0.54 Post-treatment 69.33 (29.28, 83.20) TNF-α Pre-treatment p = 0.24 Post-treatment 11.06 (7.31, 12.53) IFN-γ Pre-treatment p = 0.31 Post-treatment 19.77 (10.45, 52.83) Between-group Comparison IL-1β Experimental p < 0.001 Control IL-6 Experimental p = 0.06 Control TNF-α Experimental p = 0.91 Control IFN-γ Experimental p = 0.01 Control Before treatment, the WORMS cartilage morphology score for the patella was 3.88 ± 1.35 in the UCB-MNCs injection group and 3.88 ± 1.52 in the control group, with no statistically significant difference between the two groups. At 6 months after treatment, the WORMS cartilage morphology score for the patella decreased to 3.40 ± 1.46 in the UCB-MNCs injection group, while it remained unchanged at 3.88 ± 1.35 in the control group. Although the UCB-MNCs injection group showed a reduction in the WORMS score after treatment, the difference between the two groups was not statistically significant (P > 0.05). (Table 8 ) Table 8 Comparison of WORMS Cartilage Morphology Scores After Different Treatments Comparison Type Group Time Point Score (Mean ± SD) t-value p-value Between-group Experimental Before treatment 3.88 ± 1.35 0.01 0.99 Control Before treatment 3.88 ± 1.52 Between-group Experimental After treatment 3.40 ± 1.46 -0.92 0.36 Control After treatment 3.80 ± 1.62 Within-group Experimental Before treatment 3.88 ± 1.35 3.74 < 0.01 Experimental After treatment 3.40 ± 1.46 Within-group Control Before treatment 3.88 ± 1.52 1.16 0.26 Control After treatment 3.80 ± 1.62 Prior to treatment, the WORMS bone marrow edema scores for the patella were 2.58 ± 1.14 in the UCB-MNCs injection group and 2.90 ± 1.22 in the control group, with no statistically significant difference between the two groups. At 6 months after treatment, the WORMS bone marrow edema score significantly decreased to 0.85 ± 0.61 in the UCB-MNCs injection group, while it reduced to 1.48 ± 0.77 in the control group. The difference between the two groups after treatment was statistically significant (P < 0.05). (Table 9 ) Table 9 Comparison of WORMS bone marrow edema scores after different treatments Time Point Group WORMS Score (Mean ± SD) t-value p-value Before treatment Experimental 2.58 ± 1.14 -0.98 0.33 Control 2.90 ± 1.22 After treatment Experimental 0.85 ± 0.61 -3.26 0.02 Control 1.48 ± 0.77 Figure 2 presents representative MRI scans from a participant in the cell-therapy group. Sagittal (Fig. 2 A) and axial (Fig. 2 B) images acquired immediately before intra-articular injection of umbilical-cord blood mononuclear cells show no appreciable change in patellar cartilage thickness one year later (Figs. 2 C and 2 D, respectively). Notably, the subchondral cystic alterations evident at baseline had regressed at the 12-month follow-up. In contrast, Fig. 3 illustrates the natural history observed in a matched control subject who received sodium hyaluronate. Comparison of sagittal sequences obtained before (Fig. 3 B) and after therapy (Fig. 3 D) reveals clear progression of cartilage loss along the femoral aspect of the patellofemoral joint, together with intensification of subchondral bone-marrow oedema, consistent with advancing patellofemoral osteoarthritis. This pattern of deterioration was representative of the majority of control participants. At 1 month after treatment, the overall clinical response rate was 84.62% in the UCB-MNCs injection group and 84.00% in the control group, with no statistically significant difference in efficacy between the two groups (P > 0.05). However, at 3, 6, and 12 months after treatment, the response rates were 76.92%, 65.38%, and 61.54% in the UCB-MNCs group, compared to 44.00%, 20.00%, and 20.00% in the HA group, respectively. Significant differences in efficacy were observed between the two groups at these time points (P < 0.05). (Table 10 ) Table 10 Comparison of clinical efficacy between the two groups before and after treatment Group n Time Point Effective Ineffective Response Rate Experimental (UCB-MNCs) 26 1 month 22 4 84.62% 3 months 20 6 76.92% 6 months 17 9 65.38% 12 months 16 10 61.54% Control (HA) 25 1 month 21 4 84.00% 3 months 11 14 44.00% 6 months 5 20 20.00% 12 months 5 20 20.00% Note: Response rate = (Effective cases / Total cases) × 100%. No serious adverse events, including life-threatening conditions or damage to vital organs, were observed during the trial. There were no occurrences of tumors, severe infections, or other adverse events requiring specific medical interventions such as treatment discontinuation, dose reduction, or symptomatic management. Self-reported abnormal symptoms and signs during the study mainly included transient exacerbation of joint pain, knee swelling, low-grade fever, and elevated blood pressure. Three adverse reactions were reported in the experimental group and two in the control group, all of which resolved spontaneously without specific treatment. One patient in the experimental group, who had elevated IL-1β and IL-6 levels before treatment, developed significantly increased joint effusion two days after intra-articular cell injection. Conventional symptomatic treatment provided little relief, and arthrocentesis was performed for drainage. Analysis of the synovial fluid revealed markedly elevated levels of IL-1β, IL-6, and IFN-γ compared to pre-treatment levels. Discussion In this prospective study, patients with early- to mid-stage PFOA received a single intra-articular injection of UCB-MNCs. Compared with controls treated with sodium hyaluronate, the UCB-MNC cohort exhibited a significantly higher clinical response rate that was sustained throughout the 12-month observation period. Visual-analogue pain scores fell markedly, and Kujala and WOMAC indices documented consistent improvement in patellofemoral function (all P < 0.01 versus baseline). Synovial-fluid levels of IL-1β, IL-6 and IFN-γ declined after cell therapy, whereas no significant cytokine modulation was observed in the hyaluronate group[ 11 – 13 ]. Although quantitative MRI did not demonstrate cartilage thickening or defect filling, UCB-MNC administration substantially attenuated subchondral bone-marrow oedema—an early morphological marker of disease progression—suggesting that the observed clinical benefits are mediated primarily by anti-inflammatory and bone-remodelling effects rather than by overt cartilage regeneration. Although MSCs are increasingly utilized in the treatment of knee osteoarthritis, their application as biological agents remains constrained by several factors. The quality and concentration of MSCs are highly dependent on the tissue source, and cells from different origins exhibit distinct characteristics; for instance, adipose-derived MSCs demonstrate poorer chondrogenic capacity and an extracellular matrix rich in type I collagen and fibronectin, suitable for soft tissue repair, whereas umbilical cord blood-derived MSCs produce a matrix dominated by type III collagen and hyaluronic acid, which is more conducive to cartilage and neural regeneration. Additionally, the processes of harvesting and preparing MSCs—such as bone marrow aspiration, density gradient centrifugation, mononuclear cell isolation, and in vitro expansion—are complex and technically variable, leading to significant heterogeneity across studies and making it difficult to draw consistent conclusions regarding their therapeutic efficacy. In contrast, UCB-MNCs have emerged as a promising alternative for knee osteoarthritis treatment, offering advantages including multi-cellular synergy, ease of sourcing, and a favorable safety profile. Comprising monocytes, lymphocytes, and a small number of stem and progenitor cells[ 5 ], UCB-MNCs exert biological effects primarily through paracrine mechanisms, secreting bioactive factors like TGF-β and IGF that play critical roles in cartilage repair: TGF-β promotes chondrogenic differentiation of MSCs, and IGF stimulates synthesis of type II collagen and proteoglycans to maintain metabolic function of bone cells[ 14 ]. Studies in rabbit osteoarthritis models have shown that UCB-MNCs combined with hyaluronic acid hydrogel can support cartilage regeneration, with cellular architecture and collagen alignment resembling those of native cartilage after 16 weeks[ 15 ]. Clinical research by Jin Wenshu et al. involving 30 patients with early to moderate knee osteoarthritis demonstrated significant reductions in WOMAC and VAS scores following two intra-articular injections of UCB-MNCs, alongside improved cartilage defects on MRI at three months and no adverse events—results consistent with the present study’s findings of pain relief, functional improvement, high clinical response rates, and sustained efficacy in patellofemoral osteoarthritis patients after UCB-MNC treatment. However, unlike previous reports, this study did not identify significant cartilage repair on MRI, a discrepancy potentially attributable to differences in imaging protocols, evaluation methods, or statistical analysis. Research has demonstrated that cytokines and exosomes secreted by UCB-MNCs can inhibit chondrocyte apoptosis and promote extracellular matrix synthesis, exhibiting efficacy comparable to culture-expanded MSCs. Our findings revealed a reduction in the expression of IL-1β, IL-6, and IFN-γ in the synovial fluid of the treatment group following UCB-MNC therapy, leading us to hypothesize that UCB-MNCs may alleviate symptoms in PFOA patients through mechanisms involving immunomodulation, paracrine signaling networks, and microenvironment remodeling [ 14 ]. Existing evidence suggests that monocytes within UCB-MNCs act synergistically with Treg cells to suppress inflammation: monocytes inhibit pro-inflammatory factors such as IL-6 via IL-10 secretion, while Treg cells suppress CD8 + T-cell activity through direct contact, consistent with the decreased IL-1β and IL-6 levels observed in our study. IFN-γ, which activates macrophages and NK cells, upregulates MHC expression, and promotes the secretion of inflammatory mediators including IL-1, IL-6, and TNF-α, can exacerbate arthritis symptoms. Notably, in one atypical responder, synovial fluid analysis showed markedly elevated levels of IL-1β, IL-6, and IFN-γ, potentially linked to IFN-γ overexpression. As a Th1 cytokine, IFN-γ may disrupt the Th1/Th2 balance and promote a pro-inflammatory microenvironment. Studies indicate that intra-articular overexpression of IRF1, a downstream target of IFN-γ, can delay arthritis progression, suggesting that targeting the IFN-γ signaling pathway may offer a therapeutic strategy. Our results also showed decreased IFN-γ expression after UCB-MNC injection, supporting the speculation that UCB-MNCs may reduce chondrocyte senescence and inflammatory cytokine release—and thereby improve PFOA symptoms—through neutralization of IFN-γ. Evaluating the functional recovery of the knee joint after UCB-MNCs treatment in a scientific, reasonable, effective, and accurate manner remains a challenge. Although a variety of scoring systems are available internationally, there is currently no universally accepted gold standard. Systems such as the Lysholm Knee Score, Oxford Knee Score, American Knee Society Score (AKS), Knee Injury and Osteoarthritis Outcome Score (KOOS), WOMAC, and HSS Knee Score were developed based on the living habits and clinical contexts of foreign patient populations[ 16 ], rendering most of them unsuitable for follow-up and evaluation in Chinese patients[ 17 , 18 ], and none provide targeted assessment of patellofemoral joint function. After comparing the differences among various scoring systems, this study adopted the Kujala Score [ 19 , 20 ], which was found to be marginally applicable in Chinese patients. It includes more sub-items focused on the patellofemoral joint and demonstrates relatively strong reliability. This study has several limitations. First, the small sample size, short follow-up period, suboptimal randomization, and single-center design limit the generalizability and robustness of the findings. These factors preclude definitive conclusions regarding the long-term efficacy and safety of UCB-MNCs in the treatment of PFOA. Second, due to constraints in clinical settings, the MRI evaluation criteria used were incomplete and lacked comprehensive objective metrics, thereby limiting the ability to visually and quantitatively assess structural repair following cell transplantation. Conclusion By analyzing changes in VAS, Kujala, and WORMS scores before and after treatment, as well as differences in cytokine expression in synovial fluid, this study infers that UCB-MNCs can improve the intra-articular immune microenvironment, suppress inflammatory responses, and modulate cartilage remodeling in PFOA patients through a multicellular synergistic mechanism, thereby alleviating symptoms. Our findings suggest that intra-articular injection of UCB-MNCs may represent an effective therapeutic strategy for mild PFOA and provide a rationale for further clinical investigation. To better characterize the properties and efficacy of existing and novel biological therapies, additional high-quality, evidence-based, and persuasive clinical studies are warranted. Abbreviations UCB-MNC: Umbilical Cord Blood-Derived Mononuclear Cell, VAS: Visual Analog Scale, WORMS: Whole-Organ Magnetic Resonance Imaging Score, PFOA: Patellofemoral Osteoarthritis, KOA: Knee Osteoarthritis, MSCs: Mesenchymal Stem Cells, NSAIDs: nonsteroidal anti-inflammatory drugs, MRI: magnetic resonance imaging, BMI: body mass index, K-L grade: Kellgren-Lawrence grade, AKS: American Knee Society Score., KOOS: Knee Injury and Osteoarthritis Outcome Score Declarations Funding This study was supported by the Shandong Medical Association Umbilical Cord Blood Clinical Research Special Fund Project (YXH2021ZX063). Competing Interests Shu-wei Jia, Qi Xu, Hong-peng Yang, Shaoda Ren, Da Song, Chengzhi Ha declare there is no conflicts of interest regarding the publication of this paper. Author Contributions SWJ, CHZ and XQ performed the study, analysed the data and drafted the manuscript. YHP, RSD, SD and XL contributed to discussion of data, writing and editing of the article. SWJ, CZH and XL contributed to conception and study design and editing of the article. All authors have seen the manuscript and approved to submit to your journal. Ethics approval and consent to participate The experiment was conducted in accordance with the Declaration of Helsinki (World Medical Association). Informed consent was obtained from the patient who participated in this study. This research was approved by the Ethical Committee of Liaocheng People's Hospital. Clinical trial number ChiCTR2500100574 Date of Registration: 11 Apr 2025 Consent to publish Not applicable. Availability of data and materials The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. Acknowledgments This study was supported by the Shandong Medical Association Umbilical Cord Blood Clinical Research Special Fund Project (YXH2021ZX063). References Crossley KM. Is patellofemoral osteoarthritis a common sequela of patellofemoral pain? Br J Sports Med. 2014;48(6):409–10. Hinman RS, Crossley KM. Patellofemoral joint osteoarthritis: an important subgroup of knee osteoarthritis. Rheumatology. 2007;46(7):1057–62. Li Z, Liu Q, Zhao C, Gao X, Han W, Stefanik JJ, Jin Q, Lin J, Zhang Y. High prevalence of patellofemoral osteoarthritis in China: a multi-center population-based osteoarthritis study. Clin Rheumatol. 2020;39(12):3615–23. Hussain SM, Neilly DW, Baliga S, Patil S, Meek R. Knee osteoarthritis: a review of management options. Scot Med J. 2016;61(1):7–16. Kim YJ, Broxmeyer HE. Immune regulatory cells in umbilical cord blood and their potential roles in transplantation tolerance. Critical reviews in oncology/hematology 2011, 79(2):112–126. Greco N, Laughlin MJ. Umbilical cord blood stem cells for myocardial repair and regeneration. Methods Mol biology (Clifton NJ). 2010;660:29–52. Song J-S, Hong K-T, Kim N-M, Park H-S, Choi N-H. Human umbilical cord blood-derived mesenchymal stem cell implantation for osteoarthritis of the knee. Arch Orthop Trauma Surg. 2020;140(4):503–9. Fuggle NR, Cooper C, Oreffo ROC, Price AJ, Kaux JF, Maheu E, Cutolo M, Honvo G, Conaghan PG, Berenbaum F, et al. Alternative and complementary therapies in osteoarthritis and cartilage repair. Aging Clin Exp Res. 2020;32(4):547–60. Song JS, Hong KT, Kim NM, Jung JY, Park HS, Lee SH, Cho YJ, Kim SJ. Implantation of allogenic umbilical cord blood-derived mesenchymal stem cells improves knee osteoarthritis outcomes: Two-year follow-up. Regenerative therapy. 2020;14:32–9. 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Stem Cells Dev. 2008;17(6):1207–20. Lee DH, Kim SA, Song J-S, Shetty AA, Kim B-H, Kim SJ. Cartilage Regeneration Using Human Umbilical Cord Blood Derived Mesenchymal Stem Cells: A Systematic Review and Meta-Analysis. Medicina 2022, 58(12). Andreeva ER, Ezdakova MI, Bobyleva PI, Andrianova IV, Ratushnyy AY, Buravkova LB. Osteogenic Commitment of MSC Is Enhanced after Interaction with Umbilical Cord Blood Mononuclear Cells In Vitro. Bull Exp Biol Med. 2021;171(4):541–6. McConnell S, Kolopack P, Davis AM. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): A Review of Its Utility and Measurement Properties. Arthritis Care Res. 2001;45(5):453–61. Marmura H, Tremblay PF, Getgood AMJ, Bryant DM. Development and Preliminary Validation of the KOOS-ACL: A Short Form Version of the KOOS for Young Active Patients With ACL Tears. Am J Sports Med. 2023;51(6):1447–56. Peat G, Duncan RC, Wood LRJ, Thomas E, Muller S. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7836364","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":555574718,"identity":"9914bb84-9cb4-4180-810b-c0bcfdbfc2fa","order_by":0,"name":"Shuwei Jia","email":"","orcid":"","institution":"Shandong Second Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shuwei","middleName":"","lastName":"Jia","suffix":""},{"id":555574719,"identity":"ac1b6347-c8d5-4c1d-a511-ed7b8da0faba","order_by":1,"name":"Qi Xu","email":"","orcid":"","institution":"Liaocheng People's 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15:37:38","extension":"html","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":134457,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7836364/v1/fd5d5188376aca0ee8e991aa.html"},{"id":97766657,"identity":"5c61ad78-87a7-4a5d-87bb-1328625d2fd4","added_by":"auto","created_at":"2025-12-09 07:19:38","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":919806,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in cytokine levels in the experimental group compared to the control group\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e Changes in IL-1β Levels in Knee Joint Synovial Fluid before and after Treatment in the Experimental and Control Groups；\u003cstrong\u003eB\u003c/strong\u003e Changes in IL-6 Levels in Knee Joint Synovial Fluid before and after Treatment in the Experimental and Control Groups；\u003cstrong\u003eC\u003c/strong\u003e Changes in TNF-α Levels in Knee Joint Synovial Fluid before and after Treatment in the Experimental and Control Groups；\u003cstrong\u003eD \u003c/strong\u003eChanges in IFN-γ Levels in Knee Joint Synovial Fluid before and after Treatment in the Experimental and Control Groups.\u003c/p\u003e","description":"","filename":"Figure1.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7836364/v1/17cead8129746e9929b06e24.jpg"},{"id":97766659,"identity":"adcd300f-5d2b-4549-9d5a-3c9c5ddf4d4d","added_by":"auto","created_at":"2025-12-09 07:19:38","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1014008,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Magnetic Resonance Imaging Before and One Year After Intra-articular Umbilical Cord Blood Mononuclear Cell Injection for the Knee\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e Sagittal magnetic resonance image before intra-articular umbilical cord blood mononuclear cell injection for the knee；\u003cstrong\u003eB \u003c/strong\u003eAxial magnetic resonance image before intra-articular umbilical cord blood mononuclear cell injection for the knee；\u003cstrong\u003eC \u003c/strong\u003eSagittal magnetic resonance image at 1 year after intra-articular umbilical cord blood mononuclear cell injection for the knee；\u003cstrong\u003eD \u003c/strong\u003eAxial magnetic resonance image at 1 year after intra-articular umbilical cord blood mononuclear cell injection for the knee.\u003c/p\u003e","description":"","filename":"Figure2.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7836364/v1/362086eb2ebdc446fe5e26d9.jpg"},{"id":97896925,"identity":"572d1add-f5f5-4f31-bc2b-4e74b34be6bf","added_by":"auto","created_at":"2025-12-10 15:37:12","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":998955,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Magnetic Resonance Imaging Before and One Year After Intra-articular Sodium Hyaluronate Injection for the Knee\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e Sagittal magnetic resonance image before intra-articular sodium hyaluronate injection for the knee； \u003cstrong\u003eB\u003c/strong\u003e Axial magnetic resonance image before intra-articular sodium hyaluronate injection for the knee；\u003cstrong\u003eC\u003c/strong\u003e Sagittal magnetic resonance image at 1 year after intra-articular sodium hyaluronate injection for the knee；\u003cstrong\u003eD\u003c/strong\u003e Axial magnetic resonance image at 1 year after intra-articular sodium hyaluronate injection for the knee.\u003c/p\u003e","description":"","filename":"Figure3.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7836364/v1/584a1a9a897bfdea98e55754.jpg"},{"id":104398454,"identity":"f2dffaa4-a76b-483f-a9fb-776b9bb4e42e","added_by":"auto","created_at":"2026-03-11 12:02:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4065900,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7836364/v1/319bbf52-1bdb-46e0-aad8-1dbf986e3c73.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Umbilical Cord Blood Mononuclear Cell Therapy for Patellofemoral Osteoarthritis: A Clinical Investigation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKnee osteoarthritis (KOA) is the most common degenerative disorder of the musculoskeletal system among middle-aged and elderly individuals. Based on the affected compartment, KOA can be classified into three subtypes: isolated tibiofemoral osteoarthritis, isolated patellofemoral osteoarthritis (PFOA), and the mixed type. PFOA is a knee disorder characterized by degenerative changes in the articular surfaces of the patella and the femoral trochlea. It primarily manifests as anterior knee pain, limited mobility, and functional impairment, significantly affecting patients' quality of life[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Current research on KOA, both domestically and internationally, has predominantly focused on tibiofemoral osteoarthritis, while studies specifically targeting PFOA remain relatively limited[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, PFOA demonstrates a high prevalence among the elderly in community settings, and its incidence is steadily increasing due to the aging population. Studies indicate that the prevalence of PFOA among adults aged 50 and above in China reaches as high as 23.9%, with rates of 20.5% in men and 25.8% in women, making it a major contributor to disability in middle-aged and older adults[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Given its distinct clinical manifestations and pathological features, along with growing research into its epidemiology, risk factors, diagnosis, and treatment, PFOA has attracted increasing attention and interest from researchers worldwide.\u003c/p\u003e\u003cp\u003eCurrently, clinical management strategies primarily include the use of nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, intra-articular injections (such as corticosteroids or hyaluronic acid), and surgical interventions. However, these approaches are largely limited to symptomatic relief and are unable to reverse cartilage degeneration or promote tissue regeneration. Moreover, long-term application may be associated with risks such as gastrointestinal injury and accelerated cartilage degradation[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Therefore, exploring a biological therapy that combines both reparative and anti-inflammatory effects has become an urgent and critical challenge in the field of osteoarthritis treatment.\u003c/p\u003e\u003cp\u003eIn recent years, UCB-MNCs have attracted significant attention in the field of regenerative medicine due to their unique biological properties. UCB-MNCs are a heterogeneous population isolated from umbilical cord blood, comprising hematopoietic stem cells, MSCs, endothelial progenitor cells, and immunomodulatory cells [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. They exhibit low immunogenicity, multi-lineage differentiation potential, and paracrine activities. Studies have demonstrated that UCB-MNCs facilitate tissue repair through multiple mechanisms: the cytokines they secrete (such as IL-10 and TGF-β) can suppress inflammatory responses and modulate the local immune microenvironment[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]; meanwhile, the mesenchymal stem cell component can either differentiate into chondrocytes or activate endogenous repair programs via paracrine signaling, thereby promoting cartilage matrix synthesis and angiogenesis[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. One clinical study reported that intra-articular injection of UCB-MNCs significantly alleviated pain and improved joint function in patients with knee osteoarthritis, with MRI evidence of partial cartilage repair and therapeutic effects lasting up to six months[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Furthermore, the successful application of UCB-MNCs in conditions such as Parkinson\u0026rsquo;s disease, myocardial repair, and ulcerative colitis underscores their potential for cross-tissue regeneration.\u003c/p\u003e\u003cp\u003eAlthough UCB-MNCs have shown promise in the treatment of KOA, their clinical application in PFOA remains exploratory. Current research predominantly focuses on generalized knee degeneration, whereas the patellofemoral joint\u0026mdash;due to its distinct biomechanics and anatomical features\u0026mdash;may exhibit unique pathological mechanisms and treatment responses compared to other KOA subtypes. Furthermore, critical parameters such as the optimal injection dose, frequency, and long-term safety of UCB-MNC therapy still require systematic evaluation. For instance, Cartistem\u0026reg;, a product developed by Medipost Corp. in South Korea based on umbilical cord blood-derived mesenchymal stem cells, relies on the invasive microfracture procedure, which may increase the risk of complications. In contrast, intra-articular injection of UCB-MNCs alone offers a less invasive alternative with potential clinical advantages[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eBased on this background, the present study aims to investigate the clinical efficacy and mechanisms of intra-articular injection of UCB-MNCs in the treatment of PFOA, with a specific focus on its effects on cartilage repair, inflammation modulation, and functional improvement. By integrating imaging outcomes, molecular biological analyses, and patient-reported outcome measures, this research seeks to provide novel strategies for the precision treatment of PFOA and to promote the diversified application of umbilical cord blood-derived resources in regenerative medicine.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eA total of 60 patients with knee osteoarthritis were recruited from the outpatient department of joint surgery at our hospital, meeting the following inclusion criteria: 1. Aged 30\u0026ndash;70 years, either sex. 2.compliance with the diagnostic criteria for patellofemoral osteoarthritis as outlined in the Chinese Guidelines for Patellofemoral Joint Disorders (2020 Edition). 3. MRI-based disease severity classified as grade I to III. 4. Adequate comprehension of the clinical trial protocol and provision of written informed consent by the participant and/or legal surrogate.. Exclusion criteria included known or suspected allergy or severe adverse reactions to the cell-based investigational product or general hypersensitivity; severe patellofemoral osteoarthritis evidenced by MRI grade IV, patellofemoral subluxation, or habitual patellar dislocation; intra-articular injection in the target knee within the past six months or corticosteroid treatment within three months or long-term use of immunosuppressive or anticoagulant medications; non-degenerative arthritic conditions such as tuberculous, neoplastic, rheumatoid, gouty, or ankylosing spondylitis-related knee involvement; infectious arthritis or dermatological manifestations like eczema around the knee; hematologic disorders such as coagulopathies; presence of malignant tumors; severe cardiac or pulmonary dysfunction or poorly controlled diabetes or other conditions considered ineligible by investigators; active infections including HBV, HCV, or HIV; poor compliance or psychiatric illness; participation in other clinical trials within the past month; lactation, pregnancy, or women of childbearing age planning pregnancy; and other circumstances deemed inappropriate for enrollment by researchers. Withdrawal and discontinuation criteria are as follows: 1. Occurrence of a serious adverse event (e.g., anaphylactic reaction) during the trial. 2. Participant-requested withdrawal. 3. Inability to complete follow-up for any reason. 4. Poor compliance or receipt of any concomitant therapy that may influence outcome assessment during the study period..\u003c/p\u003e\u003cp\u003eBased on an a priori sample size estimation conducted using G*Power software, the required sample size for this study was determined. The analysis was configured with a significance level (α) of 0.05 and a statistical power (1 \u0026ndash; β) of 0.95 for a one-tailed test. The independent two-sample t-test was selected as the statistical method. Referring to previous experience and relevant domestic and international literature, and accounting for anticipated participant dropout, the number of eligible outpatients available at the study site, practical treatment and follow-up conditions, as well as statistical requirements, a medium-to-large effect size (d\u0026thinsp;=\u0026thinsp;0.72) was specified. The calculation yielded a total sample size of 50 participants.\u003c/p\u003e\u003cp\u003eThe cells used in this study were provided by the Shandong Umbilical Cord Blood Bank. Prior to use, all cells underwent comprehensive analysis following separation, purification, and packaging processes to characterize their biological properties, assess viability, and confirm the absence of contamination, thereby ensuring clinical safety for therapeutic application. This study was conducted in accordance with the World Medical Association Declaration of Helsinki and approved by the Ethical Committee of Liaocheng People's Hospital. Informed consent was obtained from the patient who participated in this study. All methods were carried out in accordance with relevant guidelines. The mean age of the patients on whom the models were based was 47.31\u0026thinsp;\u0026plusmn;\u0026thinsp;6.25 years (range 32\u0026ndash;65 years).\u003c/p\u003e\u003cp\u003eParticipants were sequentially enrolled and randomized into two groups based on their outpatient visit time, with 30 subjects in each group. The experimental group received intra-articular injections of UCB-MNCs at a dose of 2\u0026times;10⁸ cells in 3 ml normal saline, administered twice with a 3-week interval, while the control group received intra-articular injections of 2 ml sodium hyaluronate (Shupaite\u0026reg;) once per week for a total of five weeks. All injections were performed under standardized aseptic conditions with the patient in a supine position and the knee extended, using the superolateral approach as the puncture site. After routine disinfection and draping, synovial fluid was aspirated and saved for analysis following joint cavity entry confirmed by loss of resistance; repeated aspiration ensured no residual fluid remained before injection. Post-injection, the needle was removed, the site was compressed and dressed, and patients were instructed to perform immediate knee movements to distribute the agent. Post-procedure care included 24 hours of non-weight-bearing activity, resuming general activities thereafter, keeping the site dry for 2 days to prevent infection, and avoiding strenuous exercise for 2 weeks.\u003c/p\u003e\u003cp\u003eIn cases of post-injection knee swelling and pain, initial management consisted of local ice application and topical flurbiprofen gel patches. For more severe pain, oral NSAIDs, such as celecoxib capsules, were added to alleviate pain and reduce swelling. If unusually significant swelling occurred, patients were advised to return to the hospital for joint aspiration followed by irrigation with normal saline.\u003c/p\u003e\u003cp\u003eFollow-ups were conducted at 1, 3, 6, and 12 months after the initial injection. The assessments included both efficacy and safety endpoints. The efficacy observation endpoints included: (a) the VAS for pain assessment; (b) the Kujala score for patellofemoral joint function evaluation, as recommended by the National Clinical Research Center for Geriatric Diseases; (c) analysis of synovial fluid: joint aspiration was routinely performed before injection, and levels of active cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and matrix metalloproteinase-13 (MMP-13), as well as glucose, albumin, and white blood cell count, were measured using enzyme-linked immunosorbent assay (ELISA) before the first injection and three weeks post-injection; (d) evaluation of cartilage degeneration and damage via knee magnetic resonance imaging (MRI), primarily using the WORMS to assess patellar cartilage morphology and bone marrow edema\u0026mdash;where cartilage morphology was graded from 0 to 6 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)and bone marrow edema was scored from 0 to 3 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e); and (e) clinical efficacy assessment using a self-designed evaluation form completed by patients at 1, 3, 6, and 12 months post-treatment, categorizing outcomes as either effective or ineffective. Safety indicators involved documentation of all self-reported adverse events throughout the study period, including their duration, severity, measures taken, outcomes, impact on the primary condition, relationship to the investigational product, and overall assessment.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCartilage Morphology Grading Criteria Based on the Whole-Organ Magnetic Resonance Imaging Score (WORMS) System\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWORMS Score\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDescription\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNormal cartilage morphology and thickness.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNormal cartilage thickness with focal hyperintensity on T2-weighted images.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePartial-thickness cartilage defect\u0026thinsp;\u0026lt;\u0026thinsp;1 cm in width.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFull-thickness cartilage defect\u0026thinsp;\u0026lt;\u0026thinsp;1 cm in width.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMultiple partial-thickness defects intermixed with areas of normal thickness,\u0026nbsp;or\u0026nbsp;a partial-thickness defect\u0026thinsp;\u0026gt;\u0026thinsp;1 cm in width but involving\u0026thinsp;\u0026lt;\u0026thinsp;75% of the region.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiffuse (\u0026gt;\u0026thinsp;75% of the region) partial-thickness cartilage loss.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMultiple areas of full-thickness cartilage loss,\u0026nbsp;or\u0026nbsp;a full-thickness defect\u0026thinsp;\u0026gt;\u0026thinsp;1 cm in width but involving\u0026thinsp;\u0026lt;\u0026thinsp;75% of the region.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiffuse (\u0026gt;\u0026thinsp;75% of the region) full-thickness cartilage loss.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBone Marrow Edema Scoring Criteria Based on the Whole-Organ Magnetic Resonance Imaging Score (WORMS)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWORMS Score\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDefinition\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo bone marrow edema signal is present in the subchondral bone.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEdema involves up to and including 25% of the subchondral bone area.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEdema involves between 25% and 50% of the subchondral bone area.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEdema involves 50% or more of the subchondral bone area.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eStatistical analysis was performed using SPSS version 25.0. Measurement data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD). Normality and homogeneity of variance were assessed for all datasets. Baseline characteristics between the experimental and control groups were compared using independent samples t-tests or Mann-Whitney U tests for continuous variables and chi-square tests for categorical variables. Post-treatment comparisons between the two groups for continuous outcomes were analyzed using independent samples t-tests or Mann-Whitney U tests, as appropriate. Within-group comparisons of efficacy outcomes before and after treatment were conducted using paired samples t-tests or Wilcoxon signed-rank tests. A two-tailed p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 60 subjects were initially recruited for the study. Following the application of inclusion and exclusion criteria, 56 participants were enrolled, with 28 assigned to each group. Over the one-year follow-up period, 51 patients completed the entire study protocol. Attrition accounted for three patients, with one loss to follow-up in the experimental group and two in the control group. Additionally, two participants were excluded during the trial\u0026mdash;one from the experimental group due to a traumatic meniscal tear requiring arthroscopic surgery, and one from the control group due to receiving other treatments for insufficient therapeutic effect, which could potentially confound the outcome assessment. Consequently, data from 51 patients were available for final analysis, including 26 in the experimental group and 25 in the control group. This sample size met the pre-trial estimated minimum requirement of 50 subjects.\u003c/p\u003e\u003cp\u003eNo significant differences were observed in the baseline characteristics, including gender, age, body mass index (BMI), duration of disease, and Kellgren-Lawrence (K-L) grade, between the two groups among the 51 patients who completed the study (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05; Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Baseline Characteristics Between the Two Groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExperimental Group (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003cp\u003eGroup (n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStatistical Value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e*p*-Value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender, Male/Female\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 / 16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 / 15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u0026sup2; = 0.013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48.53\u0026thinsp;\u0026plusmn;\u0026thinsp;7.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46.04\u0026thinsp;\u0026plusmn;\u0026thinsp;4.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e*t*\u0026nbsp;= 1.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI, kg/m\u0026sup2;\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25.47\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e*t*\u0026nbsp;= 1.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMRI Grade, Ⅰ/Ⅱ/Ⅲ\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 / 6 / 15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 / 8 / 12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u0026sup2; = 0.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMRI Grade, Ⅰ/Ⅱ/Ⅲ\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.78\u0026thinsp;\u0026plusmn;\u0026thinsp;4.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.40\u0026thinsp;\u0026plusmn;\u0026thinsp;4.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e*t*\u0026nbsp;= 1.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eNo significant difference was observed in the VAS scores between the two groups before treatment (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), indicating comparable baseline characteristics. At the 1-month follow-up, both groups showed a reduction in VAS scores compared to their respective baseline levels, with no statistically significant difference between the groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), demonstrating that both interventions were effective in alleviating pain symptoms in patients with patellofemoral osteoarthritis. However, at the subsequent follow-up time points (3, 6, and 12 months), the experimental group exhibited significantly greater pain reduction compared to the control group, and these differences were statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), suggesting a superior and sustained analgesic effect of the experimental treatment over the conventional approach (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of VAS Scores Between the Two Groups at Different Time Points After Treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eTime Point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eVAS Score (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e*t*-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e*p*-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c3\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-1.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c3\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003e1 Month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c3\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003e3 Months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-4.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c3\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003e6 Months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-6.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.55\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" morerows=\"1\" nameend=\"c3\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003e12 Months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-7.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePrior to treatment, the Kujala scores were 67.58\u0026thinsp;\u0026plusmn;\u0026thinsp;6.68 in the experimental group and 66.84\u0026thinsp;\u0026plusmn;\u0026thinsp;7.48 in the control group, with no statistically significant difference between the two groups (t\u0026thinsp;=\u0026thinsp;0.33; p\u0026thinsp;=\u0026thinsp;0.71). After treatment, follow-up assessments at 1, 3, 6, and 12 months revealed that the Kujala scores in the experimental group gradually improved (75.85\u0026thinsp;\u0026plusmn;\u0026thinsp;6.72; 77.15\u0026thinsp;\u0026plusmn;\u0026thinsp;6.36; 78.19\u0026thinsp;\u0026plusmn;\u0026thinsp;6.30; 78.27\u0026thinsp;\u0026plusmn;\u0026thinsp;6.28), indicating that UCB-MNCs injection progressively alleviated knee pain symptoms and enhanced joint function in patients with patellofemoral arthritis. In contrast, the hyaluronic acid treatment group showed an initial increase in the Kujala score at 1 month post-treatment (76.20\u0026thinsp;\u0026plusmn;\u0026thinsp;7.00), but the scores gradually decreased thereafter (70.92\u0026thinsp;\u0026plusmn;\u0026thinsp;8.16; 70.28\u0026thinsp;\u0026plusmn;\u0026thinsp;7.36; 69.08\u0026thinsp;\u0026plusmn;\u0026thinsp;7.49), suggesting that while hyaluronic acid treatment provided short-term symptomatic relief, its long-term efficacy was limited. (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Kujala Scores at 1, 3, 6, and 12 Months After Different Treatments\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTime Point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eKujala Score (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBefore Treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e67.58\u0026thinsp;\u0026plusmn;\u0026thinsp;6.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66.84\u0026thinsp;\u0026plusmn;\u0026thinsp;7.48\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1 Month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e75.85\u0026thinsp;\u0026plusmn;\u0026thinsp;6.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76.20\u0026thinsp;\u0026plusmn;\u0026thinsp;6.97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e3 Months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e77.15\u0026thinsp;\u0026plusmn;\u0026thinsp;6.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e3.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70.92\u0026thinsp;\u0026plusmn;\u0026thinsp;8.16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e6 Months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e78.19\u0026thinsp;\u0026plusmn;\u0026thinsp;6.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e4.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e70.28\u0026thinsp;\u0026plusmn;\u0026thinsp;7.36\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 Months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e78.27\u0026thinsp;\u0026plusmn;\u0026thinsp;6.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e4.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e69.08\u0026thinsp;\u0026plusmn;\u0026thinsp;7.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePrior to treatment, statistical analysis of IL-1β, IL-6, TNF-α, and IFN-γ levels in the synovial fluid of both patient groups showed no significant differences (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), indicating comparable baseline levels between the experimental and control groups. Since the distribution of pre- and post-treatment differences in IL-1β, IL-6, TNF-α, and IFN-γ was not normal, the Wilcoxon signed-rank test was applied, and interquartile range was used to describe changes in cytokine levels. In the experimental group, IL-1β, IL-6, and IFN-γ levels decreased significantly after treatment (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), while no significant change was observed in TNF-α (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In contrast, the control group showed no statistically significant changes in any of the cytokines (IL-1β, IL-6, TNF-α, or IFN-γ; P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). After treatment, differences between the experimental and control groups were statistically significant for IL-1β, IL-6, and IFN-γ (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), but not for TNF-α. (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Kujala scores at different time points after treatment between the two groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eKujala score (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67.58\u0026thinsp;\u0026plusmn;\u0026thinsp;6.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66.84\u0026thinsp;\u0026plusmn;\u0026thinsp;7.48\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1 month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75.85\u0026thinsp;\u0026plusmn;\u0026thinsp;6.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.85\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e76.20\u0026thinsp;\u0026plusmn;\u0026thinsp;6.97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e3 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77.15\u0026thinsp;\u0026plusmn;\u0026thinsp;6.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e3.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70.92\u0026thinsp;\u0026plusmn;\u0026thinsp;8.16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.19\u0026thinsp;\u0026plusmn;\u0026thinsp;6.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e4.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70.28\u0026thinsp;\u0026plusmn;\u0026thinsp;7.36\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.27\u0026thinsp;\u0026plusmn;\u0026thinsp;6.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e4.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69.08\u0026thinsp;\u0026plusmn;\u0026thinsp;7.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eStatistical analysis of the baseline concentrations of IL-1β, IL-6, TNF-α and IFN-γ in the synovial fluid revealed no significant inter-group differences (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), confirming that the trial and control groups were comparable before intervention. Because the pre\u0026ndash;post-treatment differences in all four cytokines deviated from a normal distribution, within-group changes were evaluated with the Wilcoxon signed-rank test and summarised with median and inter-quartile range. After therapy, IL-1β, IL-6 and IFN-γ concentrations in the trial group fell markedly, and the pre- versus post-treatment differences were statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). TNF-α showed a modest decrease in the trial group and a slight increase in controls; neither change reached significance (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). As illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the trial group exhibited pronounced reductions in IL-1β, IL-6 and IFN-γ, whereas levels in the control group remained essentially unchanged or marginally increased. Although TNF-α moved in opposite directions in the two groups, the magnitude of change was small. Consequently, no significant pre\u0026ndash;post variations in IL-1β, IL-6, TNF-α or IFN-γ were detected in the control group (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Between-group comparison after treatment demonstrated significantly lower IL-1β, IL-6 and IFN-γ concentrations in the trial group than in controls (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), whereas the inter-group difference in TNF-α was not significant.(Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of changes in cytokine levels after different treatments\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComparison\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCytokine\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLevel (Median, IQR)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eStatistical Significance\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eBaseline Comparison\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIL-1β\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.98 (7.96, 15.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.94\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.63 (8.07, 12.73)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIL-6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e65.09 (32.07, 93.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.73\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e65.86 (27.76, 82.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTNF-α\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.76 (6.93, 18.99)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.07\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.31 (5.05, 15.06)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIFN-γ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21.28 (13.39, 27.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.64\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.63 (9.57, 49.29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWithin-group Changes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e\u003cp\u003e\u003cb\u003eExperimental Group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIL-1β\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.93 (4.62, 8.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIL-6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e42.11 (19.49, 60.49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTNF-α\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.17\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.21 (6.76, 15.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIFN-γ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.05 (7.89, 17.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e\u003cp\u003e\u003cb\u003eControl Group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIL-1β\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.46\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.86 (8.56, 14.84)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIL-6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.54\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e69.33 (29.28, 83.20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTNF-α\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.24\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.06 (7.31, 12.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIFN-γ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.31\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost-treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19.77 (10.45, 52.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBetween-group Comparison\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIL-1β\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIL-6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.06\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTNF-α\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.91\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIFN-γ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBefore treatment, the WORMS cartilage morphology score for the patella was 3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35 in the UCB-MNCs injection group and 3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52 in the control group, with no statistically significant difference between the two groups. At 6 months after treatment, the WORMS cartilage morphology score for the patella decreased to 3.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46 in the UCB-MNCs injection group, while it remained unchanged at 3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35 in the control group. Although the UCB-MNCs injection group showed a reduction in the WORMS score after treatment, the difference between the two groups was not statistically significant (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of WORMS Cartilage Morphology Scores After Different Treatments\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eComparison Type\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTime Point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eScore (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eBetween-group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eBetween-group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAfter treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.36\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAfter treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eWithin-group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e3.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAfter treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.40\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eWithin-group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBefore treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAfter treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePrior to treatment, the WORMS bone marrow edema scores for the patella were 2.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14 in the UCB-MNCs injection group and 2.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22 in the control group, with no statistically significant difference between the two groups. At 6 months after treatment, the WORMS bone marrow edema score significantly decreased to 0.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61 in the UCB-MNCs injection group, while it reduced to 1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77 in the control group. The difference between the two groups after treatment was statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). (Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of WORMS bone marrow edema scores after different treatments\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eTime Point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eWORMS Score (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eBefore treatment\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e2.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e2.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eAfter treatment\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eExperimental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e0.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e-3.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eControl\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e1.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents representative MRI scans from a participant in the cell-therapy group. Sagittal (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA) and axial (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) images acquired immediately before intra-articular injection of umbilical-cord blood mononuclear cells show no appreciable change in patellar cartilage thickness one year later (Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD, respectively). Notably, the subchondral cystic alterations evident at baseline had regressed at the 12-month follow-up. In contrast, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e illustrates the natural history observed in a matched control subject who received sodium hyaluronate. Comparison of sagittal sequences obtained before (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB) and after therapy (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD) reveals clear progression of cartilage loss along the femoral aspect of the patellofemoral joint, together with intensification of subchondral bone-marrow oedema, consistent with advancing patellofemoral osteoarthritis. This pattern of deterioration was representative of the majority of control participants.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAt 1 month after treatment, the overall clinical response rate was 84.62% in the UCB-MNCs injection group and 84.00% in the control group, with no statistically significant difference in efficacy between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, at 3, 6, and 12 months after treatment, the response rates were 76.92%, 65.38%, and 61.54% in the UCB-MNCs group, compared to 44.00%, 20.00%, and 20.00% in the HA group, respectively. Significant differences in efficacy were observed between the two groups at these time points (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). (Table\u0026nbsp;\u003cspan refid=\"Tab10\" class=\"InternalRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab10\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 10\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of clinical efficacy between the two groups before and after treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTime Point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eEffective\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIneffective\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eResponse Rate\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eExperimental\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(UCB-MNCs)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e84.62%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e76.92%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e65.38%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e61.54%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eControl (HA)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 month\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e84.00%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e44.00%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e20.00%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e20.00%\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eNote: Response rate = (Effective cases / Total cases) \u0026times; 100%.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eNo serious adverse events, including life-threatening conditions or damage to vital organs, were observed during the trial. There were no occurrences of tumors, severe infections, or other adverse events requiring specific medical interventions such as treatment discontinuation, dose reduction, or symptomatic management. Self-reported abnormal symptoms and signs during the study mainly included transient exacerbation of joint pain, knee swelling, low-grade fever, and elevated blood pressure. Three adverse reactions were reported in the experimental group and two in the control group, all of which resolved spontaneously without specific treatment. One patient in the experimental group, who had elevated IL-1β and IL-6 levels before treatment, developed significantly increased joint effusion two days after intra-articular cell injection. Conventional symptomatic treatment provided little relief, and arthrocentesis was performed for drainage. Analysis of the synovial fluid revealed markedly elevated levels of IL-1β, IL-6, and IFN-γ compared to pre-treatment levels.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this prospective study, patients with early- to mid-stage PFOA received a single intra-articular injection of UCB-MNCs. Compared with controls treated with sodium hyaluronate, the UCB-MNC cohort exhibited a significantly higher clinical response rate that was sustained throughout the 12-month observation period. Visual-analogue pain scores fell markedly, and Kujala and WOMAC indices documented consistent improvement in patellofemoral function (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.01 versus baseline). Synovial-fluid levels of IL-1β, IL-6 and IFN-γ declined after cell therapy, whereas no significant cytokine modulation was observed in the hyaluronate group[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Although quantitative MRI did not demonstrate cartilage thickening or defect filling, UCB-MNC administration substantially attenuated subchondral bone-marrow oedema\u0026mdash;an early morphological marker of disease progression\u0026mdash;suggesting that the observed clinical benefits are mediated primarily by anti-inflammatory and bone-remodelling effects rather than by overt cartilage regeneration.\u003c/p\u003e\u003cp\u003eAlthough MSCs are increasingly utilized in the treatment of knee osteoarthritis, their application as biological agents remains constrained by several factors. The quality and concentration of MSCs are highly dependent on the tissue source, and cells from different origins exhibit distinct characteristics; for instance, adipose-derived MSCs demonstrate poorer chondrogenic capacity and an extracellular matrix rich in type I collagen and fibronectin, suitable for soft tissue repair, whereas umbilical cord blood-derived MSCs produce a matrix dominated by type III collagen and hyaluronic acid, which is more conducive to cartilage and neural regeneration. Additionally, the processes of harvesting and preparing MSCs\u0026mdash;such as bone marrow aspiration, density gradient centrifugation, mononuclear cell isolation, and in vitro expansion\u0026mdash;are complex and technically variable, leading to significant heterogeneity across studies and making it difficult to draw consistent conclusions regarding their therapeutic efficacy. In contrast, UCB-MNCs have emerged as a promising alternative for knee osteoarthritis treatment, offering advantages including multi-cellular synergy, ease of sourcing, and a favorable safety profile. Comprising monocytes, lymphocytes, and a small number of stem and progenitor cells[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], UCB-MNCs exert biological effects primarily through paracrine mechanisms, secreting bioactive factors like TGF-β and IGF that play critical roles in cartilage repair: TGF-β promotes chondrogenic differentiation of MSCs, and IGF stimulates synthesis of type II collagen and proteoglycans to maintain metabolic function of bone cells[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Studies in rabbit osteoarthritis models have shown that UCB-MNCs combined with hyaluronic acid hydrogel can support cartilage regeneration, with cellular architecture and collagen alignment resembling those of native cartilage after 16 weeks[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Clinical research by Jin Wenshu et al. involving 30 patients with early to moderate knee osteoarthritis demonstrated significant reductions in WOMAC and VAS scores following two intra-articular injections of UCB-MNCs, alongside improved cartilage defects on MRI at three months and no adverse events\u0026mdash;results consistent with the present study\u0026rsquo;s findings of pain relief, functional improvement, high clinical response rates, and sustained efficacy in patellofemoral osteoarthritis patients after UCB-MNC treatment. However, unlike previous reports, this study did not identify significant cartilage repair on MRI, a discrepancy potentially attributable to differences in imaging protocols, evaluation methods, or statistical analysis.\u003c/p\u003e\u003cp\u003eResearch has demonstrated that cytokines and exosomes secreted by UCB-MNCs can inhibit chondrocyte apoptosis and promote extracellular matrix synthesis, exhibiting efficacy comparable to culture-expanded MSCs. Our findings revealed a reduction in the expression of IL-1β, IL-6, and IFN-γ in the synovial fluid of the treatment group following UCB-MNC therapy, leading us to hypothesize that UCB-MNCs may alleviate symptoms in PFOA patients through mechanisms involving immunomodulation, paracrine signaling networks, and microenvironment remodeling [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Existing evidence suggests that monocytes within UCB-MNCs act synergistically with Treg cells to suppress inflammation: monocytes inhibit pro-inflammatory factors such as IL-6 via IL-10 secretion, while Treg cells suppress CD8\u0026thinsp;+\u0026thinsp;T-cell activity through direct contact, consistent with the decreased IL-1β and IL-6 levels observed in our study. IFN-γ, which activates macrophages and NK cells, upregulates MHC expression, and promotes the secretion of inflammatory mediators including IL-1, IL-6, and TNF-α, can exacerbate arthritis symptoms. Notably, in one atypical responder, synovial fluid analysis showed markedly elevated levels of IL-1β, IL-6, and IFN-γ, potentially linked to IFN-γ overexpression. As a Th1 cytokine, IFN-γ may disrupt the Th1/Th2 balance and promote a pro-inflammatory microenvironment. Studies indicate that intra-articular overexpression of IRF1, a downstream target of IFN-γ, can delay arthritis progression, suggesting that targeting the IFN-γ signaling pathway may offer a therapeutic strategy. Our results also showed decreased IFN-γ expression after UCB-MNC injection, supporting the speculation that UCB-MNCs may reduce chondrocyte senescence and inflammatory cytokine release\u0026mdash;and thereby improve PFOA symptoms\u0026mdash;through neutralization of IFN-γ.\u003c/p\u003e\u003cp\u003eEvaluating the functional recovery of the knee joint after UCB-MNCs treatment in a scientific, reasonable, effective, and accurate manner remains a challenge. Although a variety of scoring systems are available internationally, there is currently no universally accepted gold standard. Systems such as the Lysholm Knee Score, Oxford Knee Score, American Knee Society Score (AKS), Knee Injury and Osteoarthritis Outcome Score (KOOS), WOMAC, and HSS Knee Score were developed based on the living habits and clinical contexts of foreign patient populations[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], rendering most of them unsuitable for follow-up and evaluation in Chinese patients[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and none provide targeted assessment of patellofemoral joint function. After comparing the differences among various scoring systems, this study adopted the Kujala Score [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], which was found to be marginally applicable in Chinese patients. It includes more sub-items focused on the patellofemoral joint and demonstrates relatively strong reliability.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, the small sample size, short follow-up period, suboptimal randomization, and single-center design limit the generalizability and robustness of the findings. These factors preclude definitive conclusions regarding the long-term efficacy and safety of UCB-MNCs in the treatment of PFOA. Second, due to constraints in clinical settings, the MRI evaluation criteria used were incomplete and lacked comprehensive objective metrics, thereby limiting the ability to visually and quantitatively assess structural repair following cell transplantation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eBy analyzing changes in VAS, Kujala, and WORMS scores before and after treatment, as well as differences in cytokine expression in synovial fluid, this study infers that UCB-MNCs can improve the intra-articular immune microenvironment, suppress inflammatory responses, and modulate cartilage remodeling in PFOA patients through a multicellular synergistic mechanism, thereby alleviating symptoms. Our findings suggest that intra-articular injection of UCB-MNCs may represent an effective therapeutic strategy for mild PFOA and provide a rationale for further clinical investigation. To better characterize the properties and efficacy of existing and novel biological therapies, additional high-quality, evidence-based, and persuasive clinical studies are warranted.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eUCB-MNC: Umbilical Cord Blood-Derived Mononuclear Cell, VAS: Visual Analog Scale, WORMS: Whole-Organ Magnetic Resonance Imaging Score, \u0026nbsp;PFOA: Patellofemoral Osteoarthritis, KOA: Knee Osteoarthritis, MSCs: Mesenchymal Stem Cells, NSAIDs: nonsteroidal anti-inflammatory drugs, MRI: magnetic resonance imaging, BMI: body mass index, K-L grade: Kellgren-Lawrence grade, AKS: American Knee Society Score., KOOS: Knee Injury and Osteoarthritis Outcome Score\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Shandong Medical Association Umbilical Cord Blood Clinical Research Special Fund Project (YXH2021ZX063).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShu-wei Jia, Qi Xu, Hong-peng Yang, Shaoda Ren, Da Song, Chengzhi Ha\u0026nbsp;declare there is no conflicts of interest regarding the publication of this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSWJ, CHZ and XQ performed the study, analysed the data and drafted the manuscript. YHP, RSD, SD and XL contributed to discussion of data, writing and editing of the article. SWJ, CZH and XL contributed to conception and study design and editing of the article. All authors have seen the manuscript and approved to submit to your journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experiment was conducted in accordance with the Declaration of Helsinki (World Medical Association). Informed consent was obtained from the patient who participated in this study. This research was approved by the\u0026nbsp;Ethical Committee of Liaocheng People\u0026apos;s Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u0026nbsp;\u003c/strong\u003eChiCTR2500100574 \u0026nbsp;Date of Registration: 11 Apr 2025\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003eThe datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Shandong Medical Association Umbilical Cord Blood Clinical Research Special Fund Project (YXH2021ZX063).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCrossley KM. Is patellofemoral osteoarthritis a common sequela of patellofemoral pain? Br J Sports Med. 2014;48(6):409\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHinman RS, Crossley KM. Patellofemoral joint osteoarthritis: an important subgroup of knee osteoarthritis. Rheumatology. 2007;46(7):1057\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi Z, Liu Q, Zhao C, Gao X, Han W, Stefanik JJ, Jin Q, Lin J, Zhang Y. High prevalence of patellofemoral osteoarthritis in China: a multi-center population-based osteoarthritis study. Clin Rheumatol. 2020;39(12):3615\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHussain SM, Neilly DW, Baliga S, Patil S, Meek R. Knee osteoarthritis: a review of management options. Scot Med J. 2016;61(1):7\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim YJ, Broxmeyer HE. 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Aging Clin Exp Res. 2020;32(4):547\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSong JS, Hong KT, Kim NM, Jung JY, Park HS, Lee SH, Cho YJ, Kim SJ. Implantation of allogenic umbilical cord blood-derived mesenchymal stem cells improves knee osteoarthritis outcomes: Two-year follow-up. Regenerative therapy. 2020;14:32\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePark Y-B, Ha C-W, Lee C-H, Yoon YC, Park Y-G. Cartilage Regeneration in Osteoarthritic Patients by a Composite of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronate Hydrogel: Results from a Clinical Trial for Safety and Proof-of-Concept with 7 Years of Extended Follow-Up. Stem Cells Translational Med. 2017;6(2):613\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFu Y, Zhang C, Yang Y, Zhou B, Yang M, Zhu G, Zhu Y. Effect of umbilical cord blood-mononuclear cells on knee osteoarthritis in rabbits. J Orthop Surg Res 2024, 19(1).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Z-W, Chen L, Hao X-R, Qu Z-A, Huang S-B, Ma X-J, Wang J-C, Wang W-M. Elevated levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and vascular endothelial growth factor in patients with knee articular cartilage injury. World J Clin Cases. 2019;7(11):1262\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHenning RJ, Shariff M, Eadula U, Alvarado F, Vasko M, Sanberg PR, Sanberg CD, Delostia V. Human Cord Blood Mononuclear Cells Decrease Cytokines and Inflammatory Cells in Acute Myocardial Infarction. Stem Cells Dev. 2008;17(6):1207\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee DH, Kim SA, Song J-S, Shetty AA, Kim B-H, Kim SJ. Cartilage Regeneration Using Human Umbilical Cord Blood Derived Mesenchymal Stem Cells: A Systematic Review and Meta-Analysis. Medicina 2022, 58(12).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAndreeva ER, Ezdakova MI, Bobyleva PI, Andrianova IV, Ratushnyy AY, Buravkova LB. Osteogenic Commitment of MSC Is Enhanced after Interaction with Umbilical Cord Blood Mononuclear Cells In Vitro. Bull Exp Biol Med. 2021;171(4):541\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcConnell S, Kolopack P, Davis AM. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): A Review of Its Utility and Measurement Properties. Arthritis Care Res. 2001;45(5):453\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarmura H, Tremblay PF, Getgood AMJ, Bryant DM. Development and Preliminary Validation of the KOOS-ACL: A Short Form Version of the KOOS for Young Active Patients With ACL Tears. Am J Sports Med. 2023;51(6):1447\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePeat G, Duncan RC, Wood LRJ, Thomas E, Muller S. Clinical features of symptomatic patellofemoral joint osteoarthritis. Arthritis Res Therapy 2012, 14(2).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCrossley KM, Bennell KL, Cowan SM, Green S. Analysis of outcome measures for persons with patellofemoral pain: which are reliable and valid?11No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated. Arch Phys Med Rehabil. 2004;85(5):815\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWatson CJ, Propps M, Ratner J, Zeigler DL. Reliability and responsiveness of the lower extremity functional scale and the anterior knee pain scale in patients with anterior knee pain. J Orthop Sports Phys Ther 2005, 35(3).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Knee Osteoarthritis, Patellofemoral Osteoarthritis, Biological Therapy, Umbilical cord blood mononuclear cells","lastPublishedDoi":"10.21203/rs.3.rs-7836364/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7836364/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eExploring the Clinical Efficacy and Mechanisms of Action of Intra-Articular Umbilical Cord Blood-Derived Mononuclear Cell (UCB-MNC) Injection in Patellofemoral Osteoarthritis (PFOA)\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA total of 60 patients with knee osteoarthritis were randomly assigned to either the experimental group (receiving UCB-MNCs injection) or the control group (receiving sodium hyaluronate injection). Follow-up assessments were conducted at 1, 3, 6, and 12 months after the initial treatment. Efficacy indicators, including the Visual Analog Scale (VAS) for pain, the patellofemoral Kujala score, cytokine expression in synovial fluid, and the Whole-Organ Magnetic Resonance Imaging Score (WORMS), as well as safety indicators, were evaluated. Statistical analysis was performed using SPSS 25.0.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 56 patients were ultimately included, with 51 completing the full follow-up. Baseline characteristics showed no statistically significant differences between the two groups before treatment. After treatment, the experimental group demonstrated superior analgesic effects compared to the control group at 3, 6, and 12 months. The Kujala scores improved gradually in the experimental group, while scores in the control group began to decline after 3 months. Significant reductions in the expression of IL-1β, IL-6, and IFN-γ in synovial fluid were observed in the experimental group, with statistically significant differences compared to the control group. At 6 months post-treatment, the WORMS bone marrow edema score decreased markedly in the experimental group, also showing a statistically significant difference from the control group. The overall clinical effectiveness rate was higher in the experimental group than in the control group at 3, 6, and 12 months after treatment. Adverse reactions in both groups were mild and self-limiting throughout the study.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eIntra-articular injection of UCB-MNCs demonstrates high clinical efficacy and sustained therapeutic effects in the treatment of PFOA, effectively alleviating pain symptoms, improving knee joint function, reducing the expression of inflammatory factors in synovial fluid, and mitigating bone marrow edema. However, further investigation is warranted to validate long-term efficacy and safety due to the current limitations in sample size and duration of follow-up.\u003c/p\u003e","manuscriptTitle":"Umbilical Cord Blood Mononuclear Cell Therapy for Patellofemoral Osteoarthritis: A Clinical Investigation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-09 07:19:32","doi":"10.21203/rs.3.rs-7836364/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"17575cc4-f1cf-4e23-8b47-33e6194e8fee","owner":[],"postedDate":"December 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-27T07:56:07+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-09 07:19:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7836364","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7836364","identity":"rs-7836364","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}