Safety and Preliminary Efficacy of Intravenous Allogeneic Adipose-Derived Mesenchymal Stem Cells (GXIPC1) in Patients with Type 1 Diabetes Mellitus: A Phase 1, Single-Arm, Open-Label Clinical Trial

Safety and Preliminary Efficacy of Intravenous Allogeneic Adipose-Derived Mesenchymal Stem Cells (GXIPC1) in Patients with Type 1 Diabetes Mellitus: A Phase 1, Single-Arm, Open-Label Clinical Trial | 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 Safety and Preliminary Efficacy of Intravenous Allogeneic Adipose-Derived Mesenchymal Stem Cells (GXIPC1) in Patients with Type 1 Diabetes Mellitus: A Phase 1, Single-Arm, Open-Label Clinical Trial Liem T. Nguyen, Hoan T. Nguyen, Kien T. Nguyen, Van T. Hoang, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8189178/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 Background Type 1 diabetes mellitus (T1DM) results from autoimmune β-cell destruction and requires lifelong insulin therapy. This study aimed to evaluate the safety and preliminary efficacy of intravenous allogeneic adipose-derived mesenchymal stem cells (MSCs, GXIPC1) in children with recent-onset T1DM. Methods In this single-arm, open-label phase 1 trial, ten children (aged ≥ 5 years) diagnosed with T1DM within the previous 12 months received a single intravenous infusion of GXIPC1 at a dose of 1×10⁶ cells/kg. The primary endpoint was safety over 6 months. Secondary endpoints included changes in HbA1c, fasting glucose, C-peptide, and daily insulin requirements at 1, 3, and 6 months after infusion. Results No treatment-related serious adverse events occurred. Six participants experienced eight mild-to-moderate adverse events (mainly mild hypoglycemia managed by insulin adjustment), none related to GXIPC1. Vital signs and laboratory parameters remained stable. Median fasting glucose decreased from 15.3 mmol/L at baseline to 5.8 mmol/L at 1 month. Daily insulin requirements decreased by 44% at 3 months (median 22.5 to 12.5 IU/day), and one participant achieved insulin independence between months 3 and 6. Median HbA1c remained stable at 3 months (7.41%) and increased slightly at 6 months (8.27%), with 30% of participants showing values below baseline and 20% below 7.5%. C-peptide levels remained stable, suggesting preserved endogenous β-cell function. Conclusions Intravenous GXIPC1 was safe and well tolerated in children with recent-onset T1DM and demonstrated encouraging signals of improved glycemic control and reduced insulin dependence. Further evaluation in randomized phase 2 trials is warranted. Type 1 diabetes mellitus adipose-derived mesenchymal stem cells glycemic control C-peptide insulin independence immunomodulation regenerative medicine Figures Figure 1 Background Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by T cell–mediated destruction of pancreatic β cells, resulting in absolute insulin deficiency and lifelong dependence on exogenous insulin therapy ( 1 , 2 ). The disease accounts for approximately 5–10% of all diabetes cases worldwide, with childhood incidence rising by 3–5% annually, most notably among children younger than 5 years ( 3 ). Its onset shows a bimodal distribution with peaks at 4–7 and 10–14 years of age, although adult-onset T1DM is not uncommon—around 40% of cases are diagnosed after age 30 ( 4 , 5 ). At diagnosis, patients typically retain approximately 40% of normal insulin secretion capacity ( 2 ), representing both a therapeutic challenge and an opportunity for intervention to preserve residual β-cell function. Despite advances in insulin formulations and technologies for glucose monitoring and delivery, optimal glycemic control remains difficult to achieve, especially in children. This lifelong dependence on daily insulin places substantial psychological, social, and economic burdens on patients and their families, including fear of hypoglycemia, dietary restrictions, and high treatment costs ( 6 ). Moreover, depending on age at onset and sex, life expectancy remains shortened by approximately 10–18 years compared with the general population ( 7 ). Current therapeutic strategies rely largely on insulin replacement, whereas islet or pancreas transplantation remains constrained by donor shortages, immunosuppressive toxicity, and procedural risks ( 8 ). These limitations underscore the need for disease-modifying interventions that preserve or restore endogenous β-cell function, thereby stabilizing metabolic control and preventing long-term complications ( 9 , 10 ). Preserving or restoring residual β-cell function early in the disease course has emerged as a critical therapeutic goal, as it improves glycemic control, reduces insulin requirements, and lowers the risk of chronic complications ( 11 , 12 ). Preclinical and clinical evidence indicates that immunomodulatory cell-based approaches could attenuate autoimmune-mediated β-cell destruction, secrete paracrine factors promoting β-cell survival and proliferation, and, under specific induction conditions, facilitate differentiation into insulin-producing cells ( 13 , 14 ). Mesenchymal stem cells (MSCs) are multipotent, nonhematopoietic cells derived from mesodermal tissues such as bone marrow, umbilical cord, and adipose tissue. These cells have primary advantages for therapy due to their immunomodulatory, anti-inflammatory, and tissue-regenerative properties ( 15 , 16 ). MSCs inhibit dendritic cell maturation, suppress T and natural killer (NK) cell activation, and promote regulatory T-cell (Treg) expansion ( 16 – 18 ). Their low immunogenicity permits allogeneic use without long-term immunosuppression ( 19 ), supporting broad applicability in immune-mediated disorders such as systemic lupus erythematosus ( 20 ), and multiple sclerosis ( 21 ). Recent clinical studies have demonstrated that MSC therapy in newly diagnosed T1DM can reduce insulin requirements and maintain C-peptide levels ( 22 – 24 ). Notably, allogeneic adipose tissue-derived MSCs (AD-MSCs) have shown favorable safety profiles and preliminary efficacy in preserving β-cell function and prolonging partial remission without immunosuppressive drugs ( 25 – 27 ). A recent meta-analysis encompassing 226 pediatric patients across 10 studies confirmed significant improvements in both C-peptide and HbA1c following MSC treatment ( 28 ). AD-MSCs possess higher immunomodulatory capacity than bone marrow or umbilical cord MSCs ( 29 ), owing to strong inhibitory effects on T-cell activation and a cytokine profile rich in IL-8, CCL5, and IDO ( 30 , 31 ). Moreover, MSCs harvested from diabetic donors often exhibit impaired viability and pro-inflammatory signatures ( 32 , 33 ), supporting the use of allogeneic AD-MSCs from healthy donors as a more reliable and effective strategy for T1DM. In this study, we investigated an allogeneic ADSC-based drug product, GXIPC1 for the treatment of T1DM. GXIPC1 is an allogeneic AD-MSC product manufactured under xeno-free, GMP-compliant conditions. It undergoes rigorous quality control and potency testing and has received regulatory approval for clinical investigation. Preclinical studies in diabetic animal models demonstrated that AD-MSCs significantly improved blood glucose regulation and preserved pancreatic islet architecture compared with control groups ( 13 , 34 , 35 ). The product was manufactured through culture expansion and distributed via cold-chain logistics for clinical application in Vietnam. The aim of this study was to evaluate the safety and preliminary therapeutic efficacy of intravenous infusion of this “off-the-shelf” allogeneic AD-MSC product in individuals recently diagnosed with T1DM. Methods Study Design This was a single-arm, phase 1 clinical trial conducted at Vinmec Times City International General Hospital, Hanoi, Vietnam, from May 2021 to December 2024. Patients Eligible participants were children aged five years or older at the time of screening, diagnosed with T1DM based on established diagnostic American Diabetes Association (ADA) criteria ( 36 ). The duration from initial diagnosis to screening was twelve months or less. At diagnosis, patients exhibited a fasting plasma glucose (FPG) of at least 7.0 mmol/L and HbA1c of 6.5% or above. Evidence of autoimmunity was required, defined as positivity for at least one T1DM-associated autoantibody, including islet cell antibody (ICA), glutamic acid decarboxylase antibody (GAD), zinc transporter 8 antibody (ZnT8), or insulin autoantibody (IAA). All participants were receiving insulin therapy at the time of enrollment and demonstrated clinical stability, with no severe acute illnesses necessitating urgent medical intervention. Written informed consent was obtained from parents or legal guardians prior to participation. Adherence to insulin therapy and all study procedures was confirmed during a two-week lead-in period, qualifying the patient for cell infusion at week 0. Participants were excluded if they exhibited evidence of renal impairment, defined as abnormal renal function or nephrotic-range proteinuria, or presented clinical signs of kidney failure or other microvascular complications. Individuals with active severe infections, including those with confirmed diagnoses of tuberculosis or positive serology for HBV, HCV, or HIV by ELISA, were also excluded. Children with significant systemic diseases, such as major cardiovascular, pulmonary, hepatic, oncologic, or neurologic disorders, did not qualify for enrollment. Further exclusion applied to those with coagulation abnormalities, including an INR greater than 1.5, a PTT exceeding 40 seconds, or a PT over 15 seconds. The use of systemic anticoagulants or corticosteroids—either current or recent—was not permitted. Patients who were concurrently participating, or had recently participated, in another investigational drug or device trial, as well as those with a known hypersensitivity to anesthetics, antibiotics, or any component used in the study procedures, were also excluded from the trial. Sample Size A total of ten patients were enrolled in this study. All participants were recruited from the pediatric endocrinology clinic at Vinmec Times City International General Hospital. Intervention GXIPC1 Production and Cryopreservation GXIPC1 were isolated from healthy donors, who were screened in accordance with Taiwan FDA and IRB standards to ensure negative results for HIV-1/2, HBV, HCV, syphilis, and exclusion for transmissible spongiform encephalopathies including Creutzfeldt–Jakob disease ( 37 ). Adipose tissue was harvested via liposuction at Hualien Tzu Chi Hospital (Hualien, Taiwan; IRB No. IRB-106-88-A), then immediately transferred to Gwo Xi (Hsinchu, Taiwan) for enzymatic digestion with collagenase. The stromal vascular fraction cells were cultured and expanded at 37°C in a 5% CO₂ incubator under xeno-free and serum-free GMP-compliant conditions (up to passage 4). Rigorous quality control was applied to every batch, including sterility, mycoplasma, and endotoxin testing, as well as immunophenotypic profiling. Morphology was assessed by phase-contrast microscopy; viability was measured with an ADAM-MC automatic cell counter (NanoEntek Inc., Seoul, South Korea). Tri-lineage differentiation capacity was analyzed by the Bioresource Collection and Research Center (FIRDI, Hsinchu, Taiwan) to confirm regulatory compliance. Final GXIPC1 product was suspended at 3 × 10⁷ ± 20% cells/mL in CryoStor® CS10 (BioLife Solutions, WA, USA), aliquoted into cryogenic vials, and stored in vapor-phase liquid nitrogen ( ≤ − 150°C) for long-term preservation. GXIPC1 Cold Chain Transportation GXIPC1 vials were shipped from Taiwan to Vietnam under import approval (No. 3705eQLD-KD) via a GDP-certified logistics provider per Taiwan FDA and PIC/S requirements. Packaging adhered to UN3373 (Biological Substance, Category B) and UN1845 (Dry Ice, IATA Class 9) regulations. Shipment integrity was maintained with high-density polystyrene insulation, dry ice, and TempTale® datalogger, with temperature recorded every 10 minutes per USP and EN 12830 guidelines. Upon arrival, procedures included container inspection, manifest matching, immediate transfer to liquid nitrogen storage, and logging of shipment data. GXIPC1 Preparation and quality control for Infusion Cell were thawed rapidly in a 37°C water bath, diluted with pre-warmed Ringer’s lactate, centrifuged at 400 × g for 4 minutes, washed to remove storage buffer, and resuspended in Ringer’s lactate. Comprehensive Quality control assays was performed to verify product integrity including assessments of cell viability (trypan blue staining), surface marker expression (flow cytometry), sterility (BacT/Alert 3D microbial detection system), mycoplasma contamination (using MycoAlert® PLUS Mycoplasma Detection Kit), and karyotype stability (G-banding). Only batches that fulfilled all predefined quality control criteria were approved for infusion. Batches that did not meet these criteria were returned to GWOXI for further evaluation or discarded. Cell viability and phenotype were reconfirmed prior to infusion according to release criteria before transport to clinical use. On the day of infusion, the selected GXPC1 product was thawed and resuspended in Ringer’s lactate using the same procedure. Cell viability, endotoxin level and mycoplasma were reconfirmed prior to infusion in accordance with the release criteria established for clinical use. For allergy prophylaxis, intravenous Solumedrol (1–2 mg/kg) and Dimedrol (1-1.5 mg/kg) were administered 30 minutes before infusion in the first patient. However, due to transient hyperglycemia and allergic reaction suspected with Solumedrol, the prophylactic use of Solumedrol was discontinued in subsequent patients while Dimedrol was continued. Each participant received a single intravenous dose of GXIPC1 at 1 × 10⁶ AD-MSCs/kg body weight, diluted in 50 mL of 0.9% normal saline, and infused over 30 minutes via peripheral venous access. Outcomes Primary Endpoint Safety endpoints were comprehensively evaluated to determine the tolerability and short-term safety profile of the investigational product. Throughout all study visits, clinical observation, laboratory analyses, and vital sign monitoring were performed. All adverse events (AEs) occurring from the time of infusion to the end of follow-up were systematically recorded and classified by severity - mild, moderate, or severe - and by their relationship to the investigational product, as related, possibly related, or unrelated. Serious adverse events (SAEs), as defined by ICH-GCP guidelines including events resulting in death, life-threatening conditions, hospitalization or extended hospitalization, persistent or significant disability, or congenital anomalies, were also specifically monitored ( 38 ). Special attention was paid to the risks of infusion-related reactions, infection, hypoglycemia, and autoimmune exacerbations. Vital signs, including body temperature, blood pressure, heart rate, and respiratory rate, were measured before, during, and immediately after infusion, as well as at all scheduled follow-up visits. Any clinically significant deviations from baseline were documented and assessed by the investigator. Laboratory safety assessments included a complete blood count with differential, liver function tests (ALT, AST, bilirubin), renal function tests (BUN, creatinine), electrolytes, and blood glucose. Immunological markers such as C-reactive protein (CRP) and autoantibody profiles were also evaluated as indicated. All laboratory parameters were interpreted relative to age-appropriate reference ranges, and any abnormalities were graded according to CTCAE v4.03 criteria ( 39 ). Secondary Endpoints Secondary endpoints encompassed key metabolic parameters integral to the management of T1DM and the evaluation of pancreatic β-cell function, including glycated hemoglobin (HbA1c), measured at baseline and at 1, 3, and 6 months post-intervention; fasting plasma glucose (FPG), assessed at the same time points; and fasting C-peptide concentrations, evaluated at 1, 3, and 6 months. Exogenous insulin requirements were systematically monitored throughout the study period, with dose reductions interpreted as evidence of improved endogenous insulin production and potential amelioration of disease pathology. Statistical Analysis Descriptive statistics were used to summarize continuous outcomes (mean ± SD or median [interquartile range (IQR)], as appropriate) and categorical outcomes (n, %). Adverse events (AEs) and serious adverse events (SAEs) were summarized in frequency tables with counts and percentages. Analyses were conducted on an intention-to-treat basis, with appropriate handling of missing data. All analyses were performed using STATA software. Results Baseline characteristics A total of 17 children were screened, of whom 10 met the inclusion and exclusion criteria and were enrolled in the study. All participants were followed for at least three months. At the six-month follow-up, one patient discontinued participation, while the remaining nine continued in the study (Fig. 1 ). [Insert Fig. 1 here] Table 1 demonstrates the baseline characteristics of the enrolled patients. The mean age was 9.6 ± 2.4 years (range 6–13), including six females (60%) and four males (40%). At baseline, the median fasting plasma glucose was 15.3 mmol/L (interquartile range [7.9–21.0] mmol/L), the median HbA1c was 7.39% (interquartile range [6.7–11.0] %), and the median C-peptide was 0.35 ng/mL (interquartile range [0.30–0.53] ng/mL). All enrolled patients tested positive for at least one T1DM-associated autoantibody: zinc transporter 8 autoantibodies (ZnT8) in 7/10, insulin autoantibodies (IAA) in 6/10, glutamic acid decarboxylase antibodies (GAD65) in 5/10, and islet cell autoantibodies (ICA) in 1/10. Table 1 Baseline Demographics and Clinical Characteristics Study ID Sex Age (years) Blood glucose (mmol/L) HbA1c (%) C-peptide (ng/mL) T1DM-associated autoantibodies 1 Male 7 27.8 6.5 0.3 ZnT8 2 Female 13 8.5 6.7 1.06 ZnT8, IAA 3 Male 9 15.6 6.6 1.69 IAA 4 Male 8 15 6.98 0.16 IAA, ICA, ZnT8 5 Female 13 7.2 7.8 0.04 IAA, ZnT8, GAD65 6 Female 11 37.7 16.4 0.3 ZnT8 7 Female 6 7.8 6.7 0.38 IAA, ZnT8, GAD65 8 Male 11 7.1 11 0.56 IAA, ZnT8, GAD65 9 Female 8 21.1 7.8 0.32 GAD65 10 Female 10 20.8 13.2 0.43 GAD65 Summary 9.6 ± 2.4 15.3 [8.0–21.0] 7.39 [6.7–11.0] 0.38 [0.30–0.88] Females: 6 (60%), Males: 4 (40%); ZnT8: 7 (70%), IAA: 6 (60%), GAD65: 5 (50%), ICA: 1 (10%) Age is presented as mean ± SD. Blood glucose, HbA1c, and C-peptide are presented as median (interquartile range). Sex and T1DM-associated autoantibodies are presented as n (%). Abbreviations: IAA = insulin autoantibodies; ICA = islet cell autoantibodies; GAD65 = anti-glutamic acid decarboxylase antibodies; ZnT8 = zinc transporter 8 autoantibodies; T1DM = type 1 diabetes mellitus. [Insert Table 1 here] GXIPC1 characterization GXIPC1 displayed the typical spindle-shaped morphology characteristic of MSCs when observed under phase-contrast microscopy (Supplementary Fig. 1A). They demonstrated multipotent differentiation potential into adipogenic, osteogenic, and chondrogenic lineages, as verified by Oil Red O, Alizarin Red, and Alcian Blue staining, respectively (Supplementary Fig. 1B). Furthermore, flow cytometry immunophenotyping confirmed that GXIPC1 cells were strongly positive for MSC surface markers CD73 (98.56%), CD90 (99.94%), and CD105 (98.26%), while hematopoietic and immune-related markers CD14 (0.12%), CD19 (0.19%), CD34 (0.18%), CD45 (0.22%), and HLA-DR (0.12%) were minimally expressed (Supplementary Fig. 1C). Taken together, these data fulfill the International Society for Cellular Therapy (ISCT) criteria for defining MSCs ( 40 ) (Supplementary Fig. 1). [Insert Supplementary Fig. 1 here] After thawing in Vietnam prior to pediatric infusion, GXIPC1 was assessed for expression of MSC markers, cell dose, viability, endotoxin and microorganism contamination (Table 2 ). The mean (± SD) expression levels of MSC markers remained high: 99.9 ± 0.07% for CD73, 99.55 ± 0.21% for CD90, and 95.61 ± 0.58% for CD105. Expression of negative markers including C45, CD34, CD11b, CD19, and HLA-DR was consistently below 0.5%. The median viable cell dose administered was 1.15 × 10⁶ cells/kg (interquartile range [IQR], 1.03–1.20 × 10⁶/kg), with a post-thaw viability median of 89.05% (IQR, 88.4–93.5%). Cytogenetic analysis confirmed normal female karyotypes across all lots. Endotoxin levels in all infusion preparations were below regulatory thresholds (< 5 EU/Kg/h), and sterility assays confirmed the absence of mycoplasma, bacterial, and fungal contamination. Table 2 Quality Control of GXIPC1 Products Patient ID CD73 (%) CD90 (%) CD105 (%) Negative marker cocktails (%) Cell Dose (×10⁶/kg) Viability (%) Karyotype Endotoxin (< 5 EU/mL) Mycoplasma Bacteria/Fungi 1 99.88 99.79 95.48 0.07 1.1 72.88 46,XX < 0.05 Negative Negative 2 99.95 99.39 95.23 0.05 1.2 88.36 46,XX < 0.05 Negative Negative 3 99.95 99.39 95.23 0.05 1.3 84.89 46,XX < 0.05 Negative Negative 4 99.95 99.39 95.23 0.05 1.0 88.89 46,XX < 0.05 Negative Negative 5 99.95 99.39 95.23 0.05 1.8 88.42 46,XX < 0.05 Negative Negative 6 99.95 99.39 95.23 0.05 1.0 89.21 46,XX < 0.05 Negative Negative 7 99.95 99.39 95.23 0.05 1.0 89.21 46,XX < 0.076 Negative Negative 8 99.8 99.8 96.0 0.5 1.2 94.9 46,XX < 0.05 Negative Negative 9 99.8 99.8 96.6 0.5 1.1 94.89 46,XX < 0.05 Negative Negative 10 99.8 99.8 96.6 0.5 1.2 94.89 46,XX < 0.061 Negative Negative Abbreviations and Notes: CD73, CD90, CD105: positive MSC surface markers (by flow cytometry). Negative marker cocktail: percentage of MSCs negative for hematopoietic and immune markers (CD34, CD45, CD11b, CD19, and HLA-DR). Cell Dose (×10⁶/kg): dose per kilogram body weight at infusion. Viability (%): percentage of living cells by trypan blue exclusion. Karyotype: conventional G-banding (all samples normal 46,XX). Endotoxin: Limulus assay result, all < 5 EU/mL. Mycoplasma and Bacteria/Fungi: testing using MycoAlert® PLUS Mycoplasma Detection Kit and sterility testing, all negative. All product lots passed minimum acceptance criteria: CD73, CD90, and CD105 expression > 95%, negative marker cocktail expression < 2%, contaminant-free, viability ≥ 70%, and normal karyotype. [Insert Table 2 here] Safety During the 6-month follow-up, no serious adverse events (SAEs) were observed among the ten treated patients. A total of eight adverse events (AEs) occurred in six patients (60%), all classified as mild or moderate in severity, with none requiring study discontinuation or hospital admission (Table 3 ). The most frequent AE was mild hypoglycemia, reported in four patients (four events, 40%). Notably, these hypoglycemic episodes occurred more than one month after cell infusion, were managed by reducing insulin doses with close monitoring, and were all considered unlikely to be directly related to GXIPC1. One case of transient hyperglycemia occurred immediately following prophylactic administration of Solu-Medrol prior to cell infusion. This event was effectively managed with insulin adjustment and close monitoring and was assessed as related to Solu-Medrol administration rather than the GXIPC1 product. Minor infections, including two cases of mild viral rhinitis in two patients (20%), were self-limiting and deemed unrelated to the study treatment. Additionally, one patient contracted COVID-19 during follow-up and recovered fully without sequelae. Table 3 Summary of Adverse Events During 6-Month Follow-up Category No. of events (no. of patients) % of patients (N = 10) Notes/Key events SAE 0 (0) 0% None reported Any AEs 8 ( 6 ) 60% 8 events in 6 patients Mild hypoglycemia 4 ( 4 ) 40% Occurred > 1 month post-infusion; all resolved with insulin adjustment; unlikely related to study product Transient hyperglycemia 1 ( 1 ) 10% Occurred after Solu-Medrol premedication; managed with insulin adjustment; not related to study product Infections 2 ( 2 ) 20% Viral rhinitis; all self-limiting; unrelated COVID-19 1 ( 1 ) 10% No sequelae; unrelated Data are presented as number of events (number of patients affected) out of total patients treated (N = 10). All AEs were mild or moderate in severity. Hypoglycemic episodes occurred > 1 month after cell infusion and were not considered directly related to the investigational product. All other events were assessed as unrelated to GXIPC1. Abbreviations: AE = adverse event, SAE = serious adverse event [Insert Table 3 here] Vital signs, including pulse rate, blood pressure, and temperature, remained stable and consistently within normal safety limits over the 6-month follow-up period. Comprehensive laboratory analyses, including complete blood counts, electrolyte profiles, hepatic, renal, and pancreatic function tests, as well as C-reactive protein levels, remained within established physiological ranges for all ten pediatric patients throughout the study period. No statistically significant deviations were observed at any follow-up visit compared with baseline (Supplementary Fig. 2- Supplementary Fig. 6). [Insert Supplementary Fig. 2 here] [Insert Supplementary Fig. 3 here] [Insert Supplementary Fig. 4 here] [Insert Supplementary Fig. 5 here] [Insert Supplementary Fig. 6 here] Preliminary efficacy HbA1C At baseline, the median HbA1c was 7.39% IQR [6.7–10.21]. At 1 month after intervention, HbA1c increased slightly to a median of 7.50% [6.60–8.19], and remained stable at 7.41% IQR [6.76–7.89] at 3 months. By 6 months, median HbA1c rose to 8.27% [7.58–8.7]. Three patients (30%) had lower HbA1c at 6 months compared to baseline, and two patients (20%) achieved an HbA1c less than 7.5% at this timepoint. Fasting blood glucose At baseline, the median fasting blood glucose was 15.3 mmol/L IQR [7.9–21.0]. At 1 month, the median was 5.8 mmol/L ([5.1–7.4]). The median fasting blood glucose levels at 3 and 6 months were 8.1 mmol/L (IQR [6.3–9.9]) and 7.9 mmol/L (IQR[5.2–8.7]), respectively. Most patients demonstrated substantial improvement by 1 month, with sustained effects observed at subsequent follow-up visits. C-Peptide Median (interpercentile range) baseline value was 0.35 ng/mL ([0.3–0.53]). At 1 month, the median was 0.19 ng/mL ([0.12–0.72]). The median at 3 months was 0.26 ng/mL ([0.14–0.77]), and at 6 months was 0.16 ng/mL ([0.05–0.55]). Overall, C-peptide values remained low and stable over follow-up period. Daily Insulin Dose The median (IQR) daily insulin dose at baseline was 22.5 IU/day ([18.8–27.3]). At 1 month, the median was 22.5 IU/day ([11–25.8]), at 3 months, median was 12.5 IU/day ([9.3–18.5]), and at 6 months, median was 23 IU/day ([15–25]). Insulin dose reductions were observed in several patients during follow-up. One patient achieved insulin independence from month 3 post-intervention and maintained this status. Detailed trends and individual patient data are shown in Supplementary Fig. 7 and Supplementary Table. [Insert Supplementary Fig. 7 here] [Insert Supplementary Table here] Discussion The findings from this phase I clinical trial demonstrate that intravenous infusion of allogeneic AD-MSCs in children with T1DM is safe and well tolerated, with preliminary evidence suggesting improvement in glycemic control. Throughout the study period, vital signs, including heart rate, blood pressure and body temperature, remained stable with no significant deviations from baseline values. Similarly, key laboratory parameters, including complete blood count, serum electrolytes such as sodium, potassium, calcium and phosphate, liver function tests including AST and ALT, renal indices such as urea and creatinine, pancreatic enzyme amylase, and the inflammatory marker C-reactive protein, all remained within normal physiological ranges. These consistent findings underscore the absence of clinically meaningful abnormalities or laboratory-related adverse effects attributable to GXIPC1 administration. No treatment-related SAEs were observed. Mild adverse events occurred in approximately 60% of participants, primarily transient hypoglycemic episodes effectively managed through standard insulin dose adjustments. One participant experienced a temporary hyperglycemic episode following pre-infusion corticosteroid administration, which was deemed unrelated to the cell therapy. Collectively, these results highlight the favorable safety profile of allogeneic AD-MSC infusion. These safety findings align with those reported by Izadi et al., who observed no treatment-related SAEs and a reduced frequency of severe hypoglycemia following autologous bone marrow-derived MSC infusion in patients with newly diagnosed T1DM ( 41 ). Similarly, the allogeneic Wharton’s jelly-derived MSC product (ProTrans) demonstrated an excellent safety profile in a phase I/II clinical trial involving adults with newly diagnosed T1DM, in which no SAEs were reported and adverse events were limited to mild upper respiratory tract infections comparable to those in the placebo group ( 42 ). This favorable safety profile is consistent with our findings in the pediatric cohort, where no hypersensitivity reactions or infusion-related complications were observed. In this phase I pediatric cohort, GXIPC1 was associated with an early HbA1c signal that was most evident at month 3 and attenuated by month 6, consistent with time‑dependent glycemic effects reported for MSC therapy. Specifically, median HbA1c was 7.39% at baseline (IQR 6.7–10.21), 7.50% at month 1 (6.60–8.19), 7.41% at month 3 (6.76–7.89), and 8.27% at month 6 (7.58–8.70), with 30% of participants below baseline at month 6 and 20% achieving HbA1c < 7.5% at that timepoint, indicating heterogeneity in durability of response. For instance, Izadi et al. reported significant HbA1c reductions at 3 months (p < 0.001) and 6 months (p = 0.015), sustained through 12 months, in a randomized trial of 21 newly diagnosed T1DM patients receiving autologous bone marrow–derived MSCs ( 41 ), providing a benchmark for early benefit and persistence in a subset of patients. Likewise, contemporary meta-analyses have shown significant HbA1c reductions at 3, 6, and 12 months with MSC therapy versus controls ( 22 ). Our observed HbA1c trajectory, showing maximal benefit at 3 months followed by a gradual rise, mirrors this temporal pattern documented across multiple MSC studies and motivates evaluation of repeat-dose regimens to sustain glycemic improvements beyond 6 months. With respect to β-cell function preservation, a slight elevation in median fasting C-peptide at 3 months post-infusion (0.35 ng/mL vs. 0.26 ng/mL at baseline) was observed, consistent with trends in previous reports. In a comprehensive meta-analysis by Habiba et al. (2024), 40.7% of patients treated with umbilical-cord-derived MSCs achieved clinical remission—defined as > 10% increase in C-peptide—compared with 11.5% in control groups (p = 0.041). Moreover, three participants in that study achieved temporary insulin independence lasting 3–20 months, comparable to one patient in our trial who maintained insulin independence from months 3 to 6 ( 23 ). These findings collectively reinforce the potential of allogeneic MSC therapy to preserve endogenous β-cell activity and reduce insulin dependence in early-stage T1DM. The reduction in daily insulin requirement in our cohort, approximately 44% at 3 months (from a median of 22.5 IU/day to 12.5 IU/day), was more pronounced than reductions reported in adult trials. Muataz et al. noted preserved insulin sensitivity without significant dose reduction ( 22 ), whereas Izadi et al. reported improvements in insulin sensitivity indices rather than absolute insulin requirements ( 41 ). This enhanced response in children may reflect the greater regenerative capacity of the pediatric immune-metabolic system, consistent with a 2020 meta-analysis indicating superior outcomes in younger patients and those with shorter disease duration ( 28 ). The temporal pattern of clinical benefit, peaking at 3 months and gradually declining thereafter, is in line with prior studies. Hwang et al. (2019) identified an optimal therapeutic window of 3–6 months post-MSC infusion, corresponding to the functional lifespan and paracrine activity of transplanted cells ( 43 ). Similarly, Lu et al. demonstrated that a two-dose infusion protocol sustained glycemic and C-peptide improvements through 12 months ( 44 ). Together, these findings support the potential utility of repeat-dose strategies to maintain durable benefits. Mechanistically, AD-MSCs are believed to enhance glycemic control through immunomodulation, trophic factor secretion, and cytoprotection. They mitigate autoimmune destruction of β-cells by upregulating regulatory T-cell activity and secreting anti-inflammatory cytokines such as IL-10 and TGF-β, while growth factors including VEGF and IGF-1 promote β-cell survival, proliferation, and islet revascularization ( 45 ). Their antioxidant and anti-apoptotic properties further protect β-cells from oxidative stress. Moreover, the low immunogenicity of AD-MSCs facilitates safe allogeneic administration without inducing significant immune reactions ( 46 , 47 ). These integrated mechanisms likely underlie the observed improvements in C-peptide, insulin sensitivity, and insulin requirements. Despite these encouraging results, several limitations warrant consideration. The small sample size (n = 10) and short follow-up duration (6 months) restrict generalizability and preclude assessment of long-term durability. Conclusion In summary, this phase I clinical trial provides preliminary evidence that GXIPC1, an allogeneic AD-MSC product, is safe and potentially efficacious in improving glycemic control and preserving residual β-cell function in children with recent-onset T1DM. While these findings support the biological plausibility and safety of allogeneic AD-MSC therapy, larger randomized controlled phase II studies with extended follow-up are warranted to validate efficacy, optimize dosing schedules, and determine long-term durability of metabolic benefits. Abbreviations AD-MSC Adipose-derived mesenchymal stem cell AE Adverse event ADA American Diabetes Association ALT Alanine aminotransferase AST Aspartate aminotransferase BUN Blood urea nitrogen CD Cluster of differentiation CRP C-reactive protein CTCAE Common Terminology Criteria for Adverse Events ELISA Enzyme-linked immunosorbent assay FPG Fasting plasma glucose GAD Glutamic acid decarboxylase antibody GDP Good Distribution Practice GMP Good Manufacturing Practice GXIPC1 Allogeneic adipose-derived mesenchymal stem cell product HbA1c Glycated hemoglobin HBV Hepatitis B virus HCV Hepatitis C virus HIV Human immunodeficiency virus IAA Insulin autoantibody ICH-GCP International Council for Harmonisation - Good Clinical Practice ICA Islet cell antibody IDO Indoleamine 2,3-dioxygenase IGF-1 Insulin-like growth factor 1 IL-8 Interleukin-8 IL-10 Interleukin-10 INR International normalized ratio IRB Institutional Review Board IU International units IQR Interquartile range ISCT International Society for Cellular Therapy kg Kilogram mL Millilitre mmol/L Millimole per litre MSC Mesenchymal stem cell NK Natural killer PIC/S Pharmaceutical Inspection Convention/Cooperative Scheme PT Prothrombin time PTT Partial thromboplastin time SAE Serious adverse event T1DM Type 1 diabetes mellitus TGF-β Transforming growth factor beta Treg Regulatory T cell UN United Nations USP United States Pharmacopeia VEGF Vascular endothelial growth factor ZnT8 Zinc transporter 8 antibody Declarations Ethics approval and consent to participate The study was conducted strictly in accordance with the ethical principles of the Declaration of Helsinki and adhered to ICH/GCP guidelines and relevant local regulations. Written informed consent was obtained from all participants or their legal guardians before enrollment. The clinical trial protocol titled “Safety and Preliminary Efficacy of Intravenous Allogeneic Adipose-Derived Mesenchymal Stem Cells (GXIPC1) in Patients with Type 1 Diabetes Mellitus: A Phase 1, Single-Arm, Open-Label Clinical Trial” was reviewed and approved by the Ethics Committee of Vinmec International Hospital, Hanoi, Vietnam (approval number 54/2020/QĐ-VMEC, approval date 04 July 2020) and also received approval from the Vietnam Ministry of Health (approval number 3463/QĐ-BYT, approval date 16 July 2021). The study is registered at ClinicalTrials.gov under identifier NCT05308836. Full financial support for participant-related costs was provided, including travel reimbursement limits per visit. Consent for publication Written informed consent for publication of anonymized individual participant data was obtained from parents or legal guardians. No identifiable personal information, images, or videos are presented in this manuscript. The consent process complied with institutional ethical standards and good clinical practice. These consent forms are maintained on file and are available upon request but not submitted with the manuscript. Competing interests All authors declare that they have no competing interests related to this work. Funding This research was funded by Gwo Xi Stem Cell Applied Technology Co., Ltd., Hsinchu, Taiwan, which supported clinical trial execution, and cell processing. The funder had no role in study design, data collection or interpretation, decision to publish, or manuscript preparation. Gwoxi Stem cell applied technology Company. Author Contribution LTN, HTN, KTN, RYL, and PCL conceptualized and designed the study. KTN, VTH, TTKP, ATPN, and TAH analyzed the data. LTN, KTN, RYL, and PCL wrote the manuscript. All the authors critically revised the manuscript and approved the final version of the manuscript. LTN, HTN, and KTN agreed to be accountable for all aspects of the work and ensured that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved. Acknowledgements We thank the participants and their families for their invaluable contribution. We gratefully acknowledge the financial support of Gwoxi Stem Cell Applied Technology Company, which enabled this study. The authors used artificial intelligence tools for grammar and spelling checks. All content, data analysis, and manuscript writing were performed by the authors. Data Availability The data supporting the conclusions of this article are available from the corresponding author upon reasonable request. References Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001;358(9277):221–9. 10.1016/S0140-6736(01)05415-0 . 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Allogeneic adipose-derived stem cells with low immunogenicity constructing tissue-engineered bone for repairing bone defects in pigs. Cell Transpl. 2012;21(12):2711–21. 10.3727/096368912X654966 . Sood V, Ricioli H, Njoku GC, Primavera R, Dietrich S, Thakor AS, et al. Adipose-derived mesenchymal stromal/stem cells in type 1 diabetes treatment. Commun Biol. 2025;8(1):1094. 10.1038/s42003-025-08244-z . Additional Declarations No competing interests reported. Supplementary Files SupplementaryFigureInformation.docx SupplementaryTable.docx SupplementaryFigure1.tiff SupplementaryFigure2.tif SupplementaryFigure3.tif SupplementaryFigure4.tif SupplementaryFigure5.tif SupplementaryFigure6.tif SupplementaryFigure7.tif Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8189178","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":574118274,"identity":"c655c846-4d46-45f6-9349-b60c9ecc7a61","order_by":0,"name":"Liem T. 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12:09:00","extension":"tiff","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":20317758,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tiff","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/b4404d94e5ec3b0de5decbb3.tiff"},{"id":100421901,"identity":"b22a158b-a196-4eb2-a98e-9d80c81e7d66","added_by":"auto","created_at":"2026-01-16 14:01:23","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":86674,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/f8387a802198f79db088a2ab.png"},{"id":100406542,"identity":"461825db-698c-4e63-981c-03adbae96e3a","added_by":"auto","created_at":"2026-01-16 13:03:00","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":157225,"visible":true,"origin":"","legend":"","description":"","filename":"b8ca0125a64f493786b73c50e74394611structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/b09a5ce91bea278791bac309.xml"},{"id":100406422,"identity":"7120aefb-d9c8-4dd3-a6fa-f0a6357b9460","added_by":"auto","created_at":"2026-01-16 13:01:49","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":174842,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/562ab2a7bcce801b0e6af254.html"},{"id":100406795,"identity":"35b79e97-2117-43e0-a5e9-cdd90dbbb2ff","added_by":"auto","created_at":"2026-01-16 13:03:22","extension":"tiff","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":425615,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCONSORT flow diagram showing participant screening, allocation, intervention, and follow-up. \u003c/strong\u003eSeventeen participants were screened. Seven did not meet criteria. Ten were enrolled and received intravenous GXIPC1 cell infusion. Follow-up at 1, 3, and 6 months. One patient lost to follow-up at 6 months due to lack of family response.\u003c/p\u003e","description":"","filename":"Figure1.tiff","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/675e81855424a26420734b70.tiff"},{"id":102350715,"identity":"0bd194ac-6dd2-4d2c-aad9-dccb9cf2c1c7","added_by":"auto","created_at":"2026-02-10 18:39:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1588227,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/09c5c5dd-60a3-42f0-8aa3-db8a54e831ba.pdf"},{"id":100406724,"identity":"bd892727-b91d-4b8e-8c3f-5ae3c9c36942","added_by":"auto","created_at":"2026-01-16 13:03:13","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16312,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/4f7bc897c6abfc20477357d5.docx"},{"id":100406037,"identity":"e2840278-64a6-4c80-abef-625e4f499437","added_by":"auto","created_at":"2026-01-16 12:34:16","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":24900,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable.docx","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/1bcdc30621c54c0e0eaf1dab.docx"},{"id":100421566,"identity":"6cb4606a-09cc-44cb-ad9d-891f4dbcfd3b","added_by":"auto","created_at":"2026-01-16 13:34:10","extension":"tiff","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":3399194,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.tiff","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/6a3da3ed23e6fa7bb9c1c923.tiff"},{"id":100406117,"identity":"33fa3ac3-b661-4753-a1a1-62d1330c1846","added_by":"auto","created_at":"2026-01-16 12:41:38","extension":"tif","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":543812,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure2.tif","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/dc73fd5dfd429376709030ff.tif"},{"id":100406794,"identity":"30b3ce56-b982-40c0-a54f-376584fba73c","added_by":"auto","created_at":"2026-01-16 13:03:21","extension":"tif","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":546848,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure3.tif","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/cc4df2ac9b39c35fd511bddf.tif"},{"id":100405660,"identity":"f967600f-28cd-4444-ab24-aa044cfa96af","added_by":"auto","created_at":"2026-01-16 12:10:45","extension":"tif","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":542412,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure4.tif","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/73d30082cea4585543f475f5.tif"},{"id":100406780,"identity":"85d31a78-aa82-4e3f-b72f-1435dd0ca04e","added_by":"auto","created_at":"2026-01-16 13:03:19","extension":"tif","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":501474,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure5.tif","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/946dedfb1d038777ed8835f1.tif"},{"id":100406746,"identity":"006362cc-7096-4851-9cfe-b9066c8b0fe6","added_by":"auto","created_at":"2026-01-16 13:03:15","extension":"tif","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":432754,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure6.tif","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/d4902511e2d100d92c5318e3.tif"},{"id":100406320,"identity":"3afc18d0-cce6-4dea-9078-b2894c50b523","added_by":"auto","created_at":"2026-01-16 13:00:19","extension":"tif","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":660774,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure7.tif","url":"https://assets-eu.researchsquare.com/files/rs-8189178/v1/5cbd579e6ee965ef745e7b8b.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety and Preliminary Efficacy of Intravenous Allogeneic Adipose-Derived Mesenchymal Stem Cells (GXIPC1) in Patients with Type 1 Diabetes Mellitus: A Phase 1, Single-Arm, Open-Label Clinical Trial","fulltext":[{"header":"Background","content":"\u003cp\u003eType 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by T cell\u0026ndash;mediated destruction of pancreatic β cells, resulting in absolute insulin deficiency and lifelong dependence on exogenous insulin therapy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The disease accounts for approximately 5\u0026ndash;10% of all diabetes cases worldwide, with childhood incidence rising by 3\u0026ndash;5% annually, most notably among children younger than 5 years (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Its onset shows a bimodal distribution with peaks at 4\u0026ndash;7 and 10\u0026ndash;14 years of age, although adult-onset T1DM is not uncommon\u0026mdash;around 40% of cases are diagnosed after age 30 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). At diagnosis, patients typically retain approximately 40% of normal insulin secretion capacity (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e), representing both a therapeutic challenge and an opportunity for intervention to preserve residual β-cell function.\u003c/p\u003e \u003cp\u003eDespite advances in insulin formulations and technologies for glucose monitoring and delivery, optimal glycemic control remains difficult to achieve, especially in children. This lifelong dependence on daily insulin places substantial psychological, social, and economic burdens on patients and their families, including fear of hypoglycemia, dietary restrictions, and high treatment costs (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Moreover, depending on age at onset and sex, life expectancy remains shortened by approximately 10\u0026ndash;18 years compared with the general population (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCurrent therapeutic strategies rely largely on insulin replacement, whereas islet or pancreas transplantation remains constrained by donor shortages, immunosuppressive toxicity, and procedural risks (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). These limitations underscore the need for disease-modifying interventions that preserve or restore endogenous β-cell function, thereby stabilizing metabolic control and preventing long-term complications (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePreserving or restoring residual β-cell function early in the disease course has emerged as a critical therapeutic goal, as it improves glycemic control, reduces insulin requirements, and lowers the risk of chronic complications (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Preclinical and clinical evidence indicates that immunomodulatory cell-based approaches could attenuate autoimmune-mediated β-cell destruction, secrete paracrine factors promoting β-cell survival and proliferation, and, under specific induction conditions, facilitate differentiation into insulin-producing cells (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Mesenchymal stem cells (MSCs) are multipotent, nonhematopoietic cells derived from mesodermal tissues such as bone marrow, umbilical cord, and adipose tissue. These cells have primary advantages for therapy due to their immunomodulatory, anti-inflammatory, and tissue-regenerative properties (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). MSCs inhibit dendritic cell maturation, suppress T and natural killer (NK) cell activation, and promote regulatory T-cell (Treg) expansion (\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Their low immunogenicity permits allogeneic use without long-term immunosuppression (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), supporting broad applicability in immune-mediated disorders such as systemic lupus erythematosus (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), and multiple sclerosis (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecent clinical studies have demonstrated that MSC therapy in newly diagnosed T1DM can reduce insulin requirements and maintain C-peptide levels (\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Notably, allogeneic adipose tissue-derived MSCs (AD-MSCs) have shown favorable safety profiles and preliminary efficacy in preserving β-cell function and prolonging partial remission without immunosuppressive drugs (\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). A recent meta-analysis encompassing 226 pediatric patients across 10 studies confirmed significant improvements in both C-peptide and HbA1c following MSC treatment (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAD-MSCs possess higher immunomodulatory capacity than bone marrow or umbilical cord MSCs (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), owing to strong inhibitory effects on T-cell activation and a cytokine profile rich in IL-8, CCL5, and IDO (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Moreover, MSCs harvested from diabetic donors often exhibit impaired viability and pro-inflammatory signatures (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), supporting the use of allogeneic AD-MSCs from healthy donors as a more reliable and effective strategy for T1DM.\u003c/p\u003e \u003cp\u003eIn this study, we investigated an allogeneic ADSC-based drug product, GXIPC1 for the treatment of T1DM. GXIPC1 is an allogeneic AD-MSC product manufactured under xeno-free, GMP-compliant conditions. It undergoes rigorous quality control and potency testing and has received regulatory approval for clinical investigation. Preclinical studies in diabetic animal models demonstrated that AD-MSCs significantly improved blood glucose regulation and preserved pancreatic islet architecture compared with control groups (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). The product was manufactured through culture expansion and distributed via cold-chain logistics for clinical application in Vietnam. The aim of this study was to evaluate the safety and preliminary therapeutic efficacy of intravenous infusion of this \u0026ldquo;off-the-shelf\u0026rdquo; allogeneic AD-MSC product in individuals recently diagnosed with T1DM.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis was a single-arm, phase 1 clinical trial conducted at Vinmec Times City International General Hospital, Hanoi, Vietnam, from May 2021 to December 2024.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatients\u003c/h3\u003e\n\u003cp\u003eEligible participants were children aged five years or older at the time of screening, diagnosed with T1DM based on established diagnostic American Diabetes Association (ADA) criteria (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). The duration from initial diagnosis to screening was twelve months or less. At diagnosis, patients exhibited a fasting plasma glucose (FPG) of at least 7.0 mmol/L and HbA1c of 6.5% or above. Evidence of autoimmunity was required, defined as positivity for at least one T1DM-associated autoantibody, including islet cell antibody (ICA), glutamic acid decarboxylase antibody (GAD), zinc transporter 8 antibody (ZnT8), or insulin autoantibody (IAA). All participants were receiving insulin therapy at the time of enrollment and demonstrated clinical stability, with no severe acute illnesses necessitating urgent medical intervention. Written informed consent was obtained from parents or legal guardians prior to participation. Adherence to insulin therapy and all study procedures was confirmed during a two-week lead-in period, qualifying the patient for cell infusion at week 0.\u003c/p\u003e \u003cp\u003eParticipants were excluded if they exhibited evidence of renal impairment, defined as abnormal renal function or nephrotic-range proteinuria, or presented clinical signs of kidney failure or other microvascular complications. Individuals with active severe infections, including those with confirmed diagnoses of tuberculosis or positive serology for HBV, HCV, or HIV by ELISA, were also excluded. Children with significant systemic diseases, such as major cardiovascular, pulmonary, hepatic, oncologic, or neurologic disorders, did not qualify for enrollment. Further exclusion applied to those with coagulation abnormalities, including an INR greater than 1.5, a PTT exceeding 40 seconds, or a PT over 15 seconds. The use of systemic anticoagulants or corticosteroids\u0026mdash;either current or recent\u0026mdash;was not permitted. Patients who were concurrently participating, or had recently participated, in another investigational drug or device trial, as well as those with a known hypersensitivity to anesthetics, antibiotics, or any component used in the study procedures, were also excluded from the trial.\u003c/p\u003e\n\u003ch3\u003eSample Size\u003c/h3\u003e\n\u003cp\u003eA total of ten patients were enrolled in this study. All participants were recruited from the pediatric endocrinology clinic at Vinmec Times City International General Hospital.\u003c/p\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eGXIPC1 Production and Cryopreservation\u003c/h2\u003e \u003cp\u003eGXIPC1 were isolated from healthy donors, who were screened in accordance with Taiwan FDA and IRB standards to ensure negative results for HIV-1/2, HBV, HCV, syphilis, and exclusion for transmissible spongiform encephalopathies including Creutzfeldt\u0026ndash;Jakob disease (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Adipose tissue was harvested via liposuction at Hualien Tzu Chi Hospital (Hualien, Taiwan; IRB No. IRB-106-88-A), then immediately transferred to Gwo Xi (Hsinchu, Taiwan) for enzymatic digestion with collagenase. The stromal vascular fraction cells were cultured and expanded at 37\u0026deg;C in a 5% CO₂ incubator under xeno-free and serum-free GMP-compliant conditions (up to passage 4).\u003c/p\u003e \u003cp\u003eRigorous quality control was applied to every batch, including sterility, mycoplasma, and endotoxin testing, as well as immunophenotypic profiling. Morphology was assessed by phase-contrast microscopy; viability was measured with an ADAM-MC automatic cell counter (NanoEntek Inc., Seoul, South Korea). Tri-lineage differentiation capacity was analyzed by the Bioresource Collection and Research Center (FIRDI, Hsinchu, Taiwan) to confirm regulatory compliance. Final GXIPC1 product was suspended at 3 \u0026times; 10⁷ \u0026plusmn; 20% cells/mL in CryoStor\u0026reg; CS10 (BioLife Solutions, WA, USA), aliquoted into cryogenic vials, and stored in vapor-phase liquid nitrogen (\u0026thinsp;\u0026le;\u0026thinsp;\u0026minus;\u0026thinsp;150\u0026deg;C) for long-term preservation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGXIPC1 Cold Chain Transportation\u003c/h2\u003e \u003cp\u003eGXIPC1 vials were shipped from Taiwan to Vietnam under import approval (No. 3705eQLD-KD) via a GDP-certified logistics provider per Taiwan FDA and PIC/S requirements. Packaging adhered to UN3373 (Biological Substance, Category B) and UN1845 (Dry Ice, IATA Class 9) regulations. Shipment integrity was maintained with high-density polystyrene insulation, dry ice, and TempTale\u0026reg; datalogger, with temperature recorded every 10 minutes per USP\u0026thinsp;\u0026lt;\u0026thinsp;1118\u0026thinsp;\u0026gt;\u0026thinsp;and EN 12830 guidelines. Upon arrival, procedures included container inspection, manifest matching, immediate transfer to liquid nitrogen storage, and logging of shipment data.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eGXIPC1 Preparation and quality control for Infusion\u003c/h3\u003e\n\u003cp\u003eCell were thawed rapidly in a 37\u0026deg;C water bath, diluted with pre-warmed Ringer\u0026rsquo;s lactate, centrifuged at 400 \u0026times; g for 4 minutes, washed to remove storage buffer, and resuspended in Ringer\u0026rsquo;s lactate. Comprehensive Quality control assays was performed to verify product integrity including assessments of cell viability (trypan blue staining), surface marker expression (flow cytometry), sterility (BacT/Alert 3D microbial detection system), mycoplasma contamination (using MycoAlert\u0026reg; PLUS Mycoplasma Detection Kit), and karyotype stability (G-banding). Only batches that fulfilled all predefined quality control criteria were approved for infusion. Batches that did not meet these criteria were returned to GWOXI for further evaluation or discarded. Cell viability and phenotype were reconfirmed prior to infusion according to release criteria before transport to clinical use.\u003c/p\u003e \u003cp\u003eOn the day of infusion, the selected GXPC1 product was thawed and resuspended in Ringer\u0026rsquo;s lactate using the same procedure. Cell viability, endotoxin level and mycoplasma were reconfirmed prior to infusion in accordance with the release criteria established for clinical use.\u003c/p\u003e \u003cp\u003eFor allergy prophylaxis, intravenous Solumedrol (1\u0026ndash;2 mg/kg) and Dimedrol (1-1.5 mg/kg) were administered 30 minutes before infusion in the first patient. However, due to transient hyperglycemia and allergic reaction suspected with Solumedrol, the prophylactic use of Solumedrol was discontinued in subsequent patients while Dimedrol was continued. Each participant received a single intravenous dose of GXIPC1 at 1 \u0026times; 10⁶ AD-MSCs/kg body weight, diluted in 50 mL of 0.9% normal saline, and infused over 30 minutes via peripheral venous access.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePrimary Endpoint\u003c/h2\u003e \u003cp\u003eSafety endpoints were comprehensively evaluated to determine the tolerability and short-term safety profile of the investigational product. Throughout all study visits, clinical observation, laboratory analyses, and vital sign monitoring were performed. All adverse events (AEs) occurring from the time of infusion to the end of follow-up were systematically recorded and classified by severity - mild, moderate, or severe - and by their relationship to the investigational product, as related, possibly related, or unrelated. Serious adverse events (SAEs), as defined by ICH-GCP guidelines including events resulting in death, life-threatening conditions, hospitalization or extended hospitalization, persistent or significant disability, or congenital anomalies, were also specifically monitored (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Special attention was paid to the risks of infusion-related reactions, infection, hypoglycemia, and autoimmune exacerbations.\u003c/p\u003e \u003cp\u003eVital signs, including body temperature, blood pressure, heart rate, and respiratory rate, were measured before, during, and immediately after infusion, as well as at all scheduled follow-up visits. Any clinically significant deviations from baseline were documented and assessed by the investigator. Laboratory safety assessments included a complete blood count with differential, liver function tests (ALT, AST, bilirubin), renal function tests (BUN, creatinine), electrolytes, and blood glucose. Immunological markers such as C-reactive protein (CRP) and autoantibody profiles were also evaluated as indicated. All laboratory parameters were interpreted relative to age-appropriate reference ranges, and any abnormalities were graded according to CTCAE v4.03 criteria (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSecondary Endpoints\u003c/h2\u003e \u003cp\u003eSecondary endpoints encompassed key metabolic parameters integral to the management of T1DM and the evaluation of pancreatic β-cell function, including glycated hemoglobin (HbA1c), measured at baseline and at 1, 3, and 6 months post-intervention; fasting plasma glucose (FPG), assessed at the same time points; and fasting C-peptide concentrations, evaluated at 1, 3, and 6 months. Exogenous insulin requirements were systematically monitored throughout the study period, with dose reductions interpreted as evidence of improved endogenous insulin production and potential amelioration of disease pathology.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eDescriptive statistics were used to summarize continuous outcomes (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or median [interquartile range (IQR)], as appropriate) and categorical outcomes (n, %). Adverse events (AEs) and serious adverse events (SAEs) were summarized in frequency tables with counts and percentages. Analyses were conducted on an intention-to-treat basis, with appropriate handling of missing data. All analyses were performed using STATA software.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics\u003c/h2\u003e \u003cp\u003eA total of 17 children were screened, of whom 10 met the inclusion and exclusion criteria and were enrolled in the study. All participants were followed for at least three months. At the six-month follow-up, one patient discontinued participation, while the remaining nine continued in the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e[Insert\u003c/em\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e demonstrates the baseline characteristics of the enrolled patients. The mean age was 9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 years (range 6\u0026ndash;13), including six females (60%) and four males (40%). At baseline, the median fasting plasma glucose was 15.3 mmol/L (interquartile range [7.9\u0026ndash;21.0] mmol/L), the median HbA1c was 7.39% (interquartile range [6.7\u0026ndash;11.0] %), and the median C-peptide was 0.35 ng/mL (interquartile range [0.30\u0026ndash;0.53] ng/mL). All enrolled patients tested positive for at least one T1DM-associated autoantibody: zinc transporter 8 autoantibodies (ZnT8) in 7/10, insulin autoantibodies (IAA) in 6/10, glutamic acid decarboxylase antibodies (GAD65) in 5/10, and islet cell autoantibodies (ICA) in 1/10.\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\u003eBaseline Demographics and Clinical Characteristics\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=\"char\" char=\".\" 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\" colname=\"c1\"\u003e \u003cp\u003eStudy ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e(years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBlood glucose (mmol/L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHbA1c\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eC-peptide\u003c/p\u003e \u003cp\u003e(ng/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eT1DM-associated autoantibodies\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eZnT8\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\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eZnT8, IAA\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\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIAA\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\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIAA, ICA, ZnT8\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\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIAA, ZnT8, GAD65\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\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eZnT8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIAA, ZnT8, GAD65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIAA, ZnT8, GAD65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGAD65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGAD65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSummary\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e15.3 [8.0\u0026ndash;21.0]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e7.39 [6.7\u0026ndash;11.0]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.38 [0.30\u0026ndash;0.88]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eFemales: 6 (60%), Males: 4 (40%); ZnT8: 7 (70%), IAA: 6 (60%), GAD65: 5 (50%), ICA: 1 (10%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cem\u003eAge is presented as mean\u003c/em\u003e\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;\u003cem\u003eSD. Blood glucose, HbA1c, and C-peptide are presented as median (interquartile range). Sex and T1DM-associated autoantibodies are presented as n (%). Abbreviations: IAA\u0026thinsp;=\u0026thinsp;insulin autoantibodies; ICA\u0026thinsp;=\u0026thinsp;islet cell autoantibodies; GAD65\u0026thinsp;=\u0026thinsp;anti-glutamic acid decarboxylase antibodies; ZnT8\u0026thinsp;=\u0026thinsp;zinc transporter 8 autoantibodies; T1DM\u0026thinsp;=\u0026thinsp;type 1 diabetes mellitus.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e[Insert\u003c/em\u003e Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eGXIPC1 characterization\u003c/h2\u003e \u003cp\u003eGXIPC1 displayed the typical spindle-shaped morphology characteristic of MSCs when observed under phase-contrast microscopy (Supplementary Fig.\u0026nbsp;1A). They demonstrated multipotent differentiation potential into adipogenic, osteogenic, and chondrogenic lineages, as verified by Oil Red O, Alizarin Red, and Alcian Blue staining, respectively (Supplementary Fig.\u0026nbsp;1B). Furthermore, flow cytometry immunophenotyping confirmed that GXIPC1 cells were strongly positive for MSC surface markers CD73 (98.56%), CD90 (99.94%), and CD105 (98.26%), while hematopoietic and immune-related markers CD14 (0.12%), CD19 (0.19%), CD34 (0.18%), CD45 (0.22%), and HLA-DR (0.12%) were minimally expressed (Supplementary Fig.\u0026nbsp;1C). Taken together, these data fulfill the International Society for Cellular Therapy (ISCT) criteria for defining MSCs (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e) (Supplementary Fig.\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e[Insert Supplementary Fig.\u0026nbsp;1 here]\u003c/h2\u003e \u003cp\u003eAfter thawing in Vietnam prior to pediatric infusion, GXIPC1 was assessed for expression of MSC markers, cell dose, viability, endotoxin and microorganism contamination (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The mean (\u0026plusmn;\u0026thinsp;SD) expression levels of MSC markers remained high: 99.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07% for CD73, 99.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.21% for CD90, and 95.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58% for CD105. Expression of negative markers including C45, CD34, CD11b, CD19, and HLA-DR was consistently below 0.5%. The median viable cell dose administered was 1.15 \u0026times; 10⁶ cells/kg (interquartile range [IQR], 1.03\u0026ndash;1.20 \u0026times; 10⁶/kg), with a post-thaw viability median of 89.05% (IQR, 88.4\u0026ndash;93.5%). Cytogenetic analysis confirmed normal female karyotypes across all lots. Endotoxin levels in all infusion preparations were below regulatory thresholds (\u0026lt;\u0026thinsp;5 EU/Kg/h), and sterility assays confirmed the absence of mycoplasma, bacterial, and fungal contamination.\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\u003eQuality Control of GXIPC1 Products\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCD73 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCD90 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCD105 (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNegative marker cocktails (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCell Dose (\u0026times;10⁶/kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eViability (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eKaryotype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eEndotoxin (\u0026lt;\u0026thinsp;5 EU/mL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMycoplasma\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBacteria/Fungi\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e72.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e88.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e84.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e88.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e88.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\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=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e89.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e95.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e89.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.076\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e96.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e94.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e96.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e94.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e99.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e96.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e94.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e46,XX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.061\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"11\"\u003e\u003cem\u003eAbbreviations and Notes: CD73, CD90, CD105: positive MSC surface markers (by flow cytometry). Negative marker cocktail: percentage of MSCs negative for hematopoietic and immune markers (CD34, CD45, CD11b, CD19, and HLA-DR). Cell Dose (\u0026times;10⁶/kg): dose per kilogram body weight at infusion. Viability (%): percentage of living cells by trypan blue exclusion. Karyotype: conventional G-banding (all samples normal 46,XX). Endotoxin: Limulus assay result, all \u0026lt;\u0026thinsp;5 EU/mL. Mycoplasma and Bacteria/Fungi: testing using MycoAlert\u0026reg; PLUS Mycoplasma Detection Kit and sterility testing, all negative. All product lots passed minimum acceptance criteria: CD73, CD90, and CD105 expression\u0026thinsp;\u0026gt;\u0026thinsp;95%, negative marker cocktail expression\u0026thinsp;\u0026lt;\u0026thinsp;2%, contaminant-free, viability\u0026thinsp;\u0026ge;\u0026thinsp;70%, and normal karyotype.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e[Insert\u003c/em\u003e Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eSafety\u003c/h2\u003e \u003cp\u003eDuring the 6-month follow-up, no serious adverse events (SAEs) were observed among the ten treated patients. A total of eight adverse events (AEs) occurred in six patients (60%), all classified as mild or moderate in severity, with none requiring study discontinuation or hospital admission (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The most frequent AE was mild hypoglycemia, reported in four patients (four events, 40%). Notably, these hypoglycemic episodes occurred more than one month after cell infusion, were managed by reducing insulin doses with close monitoring, and were all considered unlikely to be directly related to GXIPC1. One case of transient hyperglycemia occurred immediately following prophylactic administration of Solu-Medrol prior to cell infusion. This event was effectively managed with insulin adjustment and close monitoring and was assessed as related to Solu-Medrol administration rather than the GXIPC1 product. Minor infections, including two cases of mild viral rhinitis in two patients (20%), were self-limiting and deemed unrelated to the study treatment. Additionally, one patient contracted COVID-19 during follow-up and recovered fully without sequelae.\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\u003eSummary of Adverse Events During 6-Month Follow-up\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo. of events\u003c/p\u003e \u003cp\u003e(no. of patients)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e% of patients (N\u0026thinsp;=\u0026thinsp;10)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNotes/Key events\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSAE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNone reported\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny AEs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 events in 6 patients\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild hypoglycemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOccurred\u0026thinsp;\u0026gt;\u0026thinsp;1 month post-infusion; all resolved with insulin adjustment; unlikely related to study product\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransient hyperglycemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOccurred after Solu-Medrol premedication; managed with insulin adjustment; not related to study product\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfections\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eViral rhinitis; all self-limiting; unrelated\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo sequelae; unrelated\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eData are presented as number of events (number of patients affected) out of total patients treated (N\u0026thinsp;=\u0026thinsp;10). All AEs were mild or moderate in severity. Hypoglycemic episodes occurred\u0026thinsp;\u0026gt;\u0026thinsp;1 month after cell infusion and were not considered directly related to the investigational product. All other events were assessed as unrelated to GXIPC1. Abbreviations: AE\u0026thinsp;=\u0026thinsp;adverse event, SAE\u0026thinsp;=\u0026thinsp;serious adverse event\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003e[Insert\u003c/em\u003e Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cem\u003ehere]\u003c/em\u003e\u003c/p\u003e \u003cp\u003eVital signs, including pulse rate, blood pressure, and temperature, remained stable and consistently within normal safety limits over the 6-month follow-up period. Comprehensive laboratory analyses, including complete blood counts, electrolyte profiles, hepatic, renal, and pancreatic function tests, as well as C-reactive protein levels, remained within established physiological ranges for all ten pediatric patients throughout the study period. No statistically significant deviations were observed at any follow-up visit compared with baseline (Supplementary Fig.\u0026nbsp;2- Supplementary Fig.\u0026nbsp;6).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e[Insert Supplementary Fig.\u0026nbsp;2 here]\u003c/h2\u003e \u003cdiv id=\"Sec20\" class=\"Section3\"\u003e \u003ch2\u003e[Insert Supplementary Fig.\u0026nbsp;3 here]\u003c/h2\u003e \u003cdiv id=\"Sec21\" class=\"Section4\"\u003e \u003ch2\u003e[Insert Supplementary Fig.\u0026nbsp;4 here]\u003c/h2\u003e \u003cp\u003e \u003cem\u003e[Insert Supplementary Fig.\u0026nbsp;5 here]\u003c/em\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section3\"\u003e \u003ch2\u003e[Insert Supplementary Fig.\u0026nbsp;6 here]\u003c/h2\u003e \u003cdiv id=\"Sec23\" class=\"Section4\"\u003e \u003ch2\u003ePreliminary efficacy\u003c/h2\u003e \u003cp\u003e \u003cb\u003eHbA1C\u003c/b\u003e \u003c/p\u003e \u003cp\u003eAt baseline, the median HbA1c was 7.39% IQR [6.7\u0026ndash;10.21]. At 1 month after intervention, HbA1c increased slightly to a median of 7.50% [6.60\u0026ndash;8.19], and remained stable at 7.41% IQR [6.76\u0026ndash;7.89] at 3 months. By 6 months, median HbA1c rose to 8.27% [7.58\u0026ndash;8.7]. Three patients (30%) had lower HbA1c at 6 months compared to baseline, and two patients (20%) achieved an HbA1c less than 7.5% at this timepoint.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section3\"\u003e \u003ch2\u003eFasting blood glucose\u003c/h2\u003e \u003cp\u003eAt baseline, the median fasting blood glucose was 15.3 mmol/L IQR [7.9\u0026ndash;21.0]. At 1 month, the median was 5.8 mmol/L ([5.1\u0026ndash;7.4]). The median fasting blood glucose levels at 3 and 6 months were 8.1 mmol/L (IQR [6.3\u0026ndash;9.9]) and 7.9 mmol/L (IQR[5.2\u0026ndash;8.7]), respectively. Most patients demonstrated substantial improvement by 1 month, with sustained effects observed at subsequent follow-up visits.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec25\" class=\"Section3\"\u003e \u003ch2\u003eC-Peptide\u003c/h2\u003e \u003cp\u003eMedian (interpercentile range) baseline value was 0.35 ng/mL ([0.3\u0026ndash;0.53]). At 1 month, the median was 0.19 ng/mL ([0.12\u0026ndash;0.72]). The median at 3 months was 0.26 ng/mL ([0.14\u0026ndash;0.77]), and at 6 months was 0.16 ng/mL ([0.05\u0026ndash;0.55]). Overall, C-peptide values remained low and stable over follow-up period.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec26\" class=\"Section2\"\u003e \u003ch2\u003eDaily Insulin Dose\u003c/h2\u003e \u003cp\u003eThe median (IQR) daily insulin dose at baseline was 22.5 IU/day ([18.8\u0026ndash;27.3]). At 1 month, the median was 22.5 IU/day ([11\u0026ndash;25.8]), at 3 months, median was 12.5 IU/day ([9.3\u0026ndash;18.5]), and at 6 months, median was 23 IU/day ([15\u0026ndash;25]). Insulin dose reductions were observed in several patients during follow-up. One patient achieved insulin independence from month 3 post-intervention and maintained this status.\u003c/p\u003e \u003cp\u003eDetailed trends and individual patient data are shown in Supplementary Fig.\u0026nbsp;7 and Supplementary Table.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section2\"\u003e \u003ch2\u003e[Insert Supplementary Fig.\u0026nbsp;7 here]\u003c/h2\u003e \u003cdiv id=\"Sec28\" class=\"Section3\"\u003e \u003ch2\u003e[Insert Supplementary Table here]\u003c/h2\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings from this phase I clinical trial demonstrate that intravenous infusion of allogeneic AD-MSCs in children with T1DM is safe and well tolerated, with preliminary evidence suggesting improvement in glycemic control.\u003c/p\u003e \u003cp\u003eThroughout the study period, vital signs, including heart rate, blood pressure and body temperature, remained stable with no significant deviations from baseline values. Similarly, key laboratory parameters, including complete blood count, serum electrolytes such as sodium, potassium, calcium and phosphate, liver function tests including AST and ALT, renal indices such as urea and creatinine, pancreatic enzyme amylase, and the inflammatory marker C-reactive protein, all remained within normal physiological ranges. These consistent findings underscore the absence of clinically meaningful abnormalities or laboratory-related adverse effects attributable to GXIPC1 administration. No treatment-related SAEs were observed. Mild adverse events occurred in approximately 60% of participants, primarily transient hypoglycemic episodes effectively managed through standard insulin dose adjustments. One participant experienced a temporary hyperglycemic episode following pre-infusion corticosteroid administration, which was deemed unrelated to the cell therapy.\u003c/p\u003e \u003cp\u003eCollectively, these results highlight the favorable safety profile of allogeneic AD-MSC infusion. These safety findings align with those reported by Izadi et al., who observed no treatment-related SAEs and a reduced frequency of severe hypoglycemia following autologous bone marrow-derived MSC infusion in patients with newly diagnosed T1DM (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). Similarly, the allogeneic Wharton\u0026rsquo;s jelly-derived MSC product (ProTrans) demonstrated an excellent safety profile in a phase I/II clinical trial involving adults with newly diagnosed T1DM, in which no SAEs were reported and adverse events were limited to mild upper respiratory tract infections comparable to those in the placebo group (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). This favorable safety profile is consistent with our findings in the pediatric cohort, where no hypersensitivity reactions or infusion-related complications were observed.\u003c/p\u003e \u003cp\u003eIn this phase I pediatric cohort, GXIPC1 was associated with an early HbA1c signal that was most evident at month 3 and attenuated by month 6, consistent with time‑dependent glycemic effects reported for MSC therapy. Specifically, median HbA1c was 7.39% at baseline (IQR 6.7\u0026ndash;10.21), 7.50% at month 1 (6.60\u0026ndash;8.19), 7.41% at month 3 (6.76\u0026ndash;7.89), and 8.27% at month 6 (7.58\u0026ndash;8.70), with 30% of participants below baseline at month 6 and 20% achieving HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;7.5% at that timepoint, indicating heterogeneity in durability of response. For instance, Izadi et al. reported significant HbA1c reductions at 3 months (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 6 months (p\u0026thinsp;=\u0026thinsp;0.015), sustained through 12 months, in a randomized trial of 21 newly diagnosed T1DM patients receiving autologous bone marrow\u0026ndash;derived MSCs (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e), providing a benchmark for early benefit and persistence in a subset of patients. Likewise, contemporary meta-analyses have shown significant HbA1c reductions at 3, 6, and 12 months with MSC therapy versus controls (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Our observed HbA1c trajectory, showing maximal benefit at 3 months followed by a gradual rise, mirrors this temporal pattern documented across multiple MSC studies and motivates evaluation of repeat-dose regimens to sustain glycemic improvements beyond 6 months.\u003c/p\u003e \u003cp\u003eWith respect to β-cell function preservation, a slight elevation in median fasting C-peptide at 3 months post-infusion (0.35 ng/mL vs. 0.26 ng/mL at baseline) was observed, consistent with trends in previous reports. In a comprehensive meta-analysis by Habiba et al. (2024), 40.7% of patients treated with umbilical-cord-derived MSCs achieved clinical remission\u0026mdash;defined as \u0026gt;\u0026thinsp;10% increase in C-peptide\u0026mdash;compared with 11.5% in control groups (p\u0026thinsp;=\u0026thinsp;0.041). Moreover, three participants in that study achieved temporary insulin independence lasting 3\u0026ndash;20 months, comparable to one patient in our trial who maintained insulin independence from months 3 to 6 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). These findings collectively reinforce the potential of allogeneic MSC therapy to preserve endogenous β-cell activity and reduce insulin dependence in early-stage T1DM.\u003c/p\u003e \u003cp\u003eThe reduction in daily insulin requirement in our cohort, approximately 44% at 3 months (from a median of 22.5 IU/day to 12.5 IU/day), was more pronounced than reductions reported in adult trials. Muataz et al. noted preserved insulin sensitivity without significant dose reduction (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), whereas Izadi et al. reported improvements in insulin sensitivity indices rather than absolute insulin requirements (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). This enhanced response in children may reflect the greater regenerative capacity of the pediatric immune-metabolic system, consistent with a 2020 meta-analysis indicating superior outcomes in younger patients and those with shorter disease duration (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe temporal pattern of clinical benefit, peaking at 3 months and gradually declining thereafter, is in line with prior studies. Hwang et al. (2019) identified an optimal therapeutic window of 3\u0026ndash;6 months post-MSC infusion, corresponding to the functional lifespan and paracrine activity of transplanted cells (\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). Similarly, Lu et al. demonstrated that a two-dose infusion protocol sustained glycemic and C-peptide improvements through 12 months (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). Together, these findings support the potential utility of repeat-dose strategies to maintain durable benefits.\u003c/p\u003e \u003cp\u003eMechanistically, AD-MSCs are believed to enhance glycemic control through immunomodulation, trophic factor secretion, and cytoprotection. They mitigate autoimmune destruction of β-cells by upregulating regulatory T-cell activity and secreting anti-inflammatory cytokines such as IL-10 and TGF-β, while growth factors including VEGF and IGF-1 promote β-cell survival, proliferation, and islet revascularization (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Their antioxidant and anti-apoptotic properties further protect β-cells from oxidative stress. Moreover, the low immunogenicity of AD-MSCs facilitates safe allogeneic administration without inducing significant immune reactions (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). These integrated mechanisms likely underlie the observed improvements in C-peptide, insulin sensitivity, and insulin requirements.\u003c/p\u003e \u003cp\u003eDespite these encouraging results, several limitations warrant consideration. The small sample size (n\u0026thinsp;=\u0026thinsp;10) and short follow-up duration (6 months) restrict generalizability and preclude assessment of long-term durability.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this phase I clinical trial provides preliminary evidence that GXIPC1, an allogeneic AD-MSC product, is safe and potentially efficacious in improving glycemic control and preserving residual β-cell function in children with recent-onset T1DM. While these findings support the biological plausibility and safety of allogeneic AD-MSC therapy, larger randomized controlled phase II studies with extended follow-up are warranted to validate efficacy, optimize dosing schedules, and determine long-term durability of metabolic benefits.\u003c/p\u003e"},{"header":"Abbreviations","content":" \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAD-MSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdipose-derived mesenchymal stem cell\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdverse event\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmerican Diabetes Association\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlanine aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAspartate aminotransferase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBUN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBlood urea nitrogen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCluster of differentiation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eC-reactive protein\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCTCAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCommon Terminology Criteria for Adverse Events\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eELISA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEnzyme-linked immunosorbent assay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFPG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFasting plasma glucose\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlutamic acid decarboxylase antibody\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGDP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGood Distribution Practice\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGMP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGood Manufacturing Practice\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGXIPC1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAllogeneic adipose-derived mesenchymal stem cell product\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHbA1c\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlycated hemoglobin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHBV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHepatitis B virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHepatitis C virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHuman immunodeficiency virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIAA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInsulin autoantibody\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICH-GCP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Council for Harmonisation - Good Clinical Practice\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIslet cell antibody\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIDO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIndoleamine 2,3-dioxygenase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIGF-1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInsulin-like growth factor 1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-8\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterleukin-8\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIL-10\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterleukin-10\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eINR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational normalized ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIRB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInstitutional Review Board\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational units\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eISCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Society for Cellular Therapy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ekg\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKilogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMillilitre\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003emmol/L\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMillimole per litre\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMesenchymal stem cell\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNK\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNatural killer\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePIC/S\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePharmaceutical Inspection Convention/Cooperative Scheme\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProthrombin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePartial thromboplastin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSerious adverse event\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eT1DM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eType 1 diabetes mellitus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTGF-β\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTransforming growth factor beta\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTreg\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRegulatory T cell\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUnited Nations\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUSP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUnited States Pharmacopeia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVEGF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVascular endothelial growth factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eZnT8\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eZinc transporter 8 antibody\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e The study was conducted strictly in accordance with the ethical principles of the Declaration of Helsinki and adhered to ICH/GCP guidelines and relevant local regulations. Written informed consent was obtained from all participants or their legal guardians before enrollment. The clinical trial protocol titled \u0026ldquo;Safety and Preliminary Efficacy of Intravenous Allogeneic Adipose-Derived Mesenchymal Stem Cells (GXIPC1) in Patients with Type 1 Diabetes Mellitus: A Phase 1, Single-Arm, Open-Label Clinical Trial\u0026rdquo; was reviewed and approved by the Ethics Committee of Vinmec International Hospital, Hanoi, Vietnam (approval number 54/2020/QĐ-VMEC, approval date 04 July 2020) and also received approval from the Vietnam Ministry of Health (approval number 3463/QĐ-BYT, approval date 16 July 2021). The study is registered at ClinicalTrials.gov under identifier NCT05308836. Full financial support for participant-related costs was provided, including travel reimbursement limits per visit.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eWritten informed consent for publication of anonymized individual participant data was obtained from parents or legal guardians. No identifiable personal information, images, or videos are presented in this manuscript. The consent process complied with institutional ethical standards and good clinical practice. These consent forms are maintained on file and are available upon request but not submitted with the manuscript.\u003c/p\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eAll authors declare that they have no competing interests related to this work.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research was funded by Gwo Xi Stem Cell Applied Technology Co., Ltd., Hsinchu, Taiwan, which supported clinical trial execution, and cell processing. The funder had no role in study design, data collection or interpretation, decision to publish, or manuscript preparation. Gwoxi Stem cell applied technology Company.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLTN, HTN, KTN, RYL, and PCL conceptualized and designed the study. KTN, VTH, TTKP, ATPN, and TAH analyzed the data. LTN, KTN, RYL, and PCL wrote the manuscript. All the authors critically revised the manuscript and approved the final version of the manuscript. LTN, HTN, and KTN agreed to be accountable for all aspects of the work and ensured that questions related to the accuracy or integrity of any part of the work were appropriately investigated and resolved.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe thank the participants and their families for their invaluable contribution. We gratefully acknowledge the financial support of Gwoxi Stem Cell Applied Technology Company, which enabled this study. The authors used artificial intelligence tools for grammar and spelling checks. All content, data analysis, and manuscript writing were performed by the authors.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the conclusions of this article are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAtkinson MA, Eisenbarth GS. 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Commun Biol. 2025;8(1):1094. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s42003-025-08244-z\u003c/span\u003e\u003cspan address=\"10.1038/s42003-025-08244-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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":"Type 1 diabetes mellitus, adipose-derived mesenchymal stem cells, glycemic control, C-peptide, insulin independence, immunomodulation, regenerative medicine","lastPublishedDoi":"10.21203/rs.3.rs-8189178/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8189178/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eType 1 diabetes mellitus (T1DM) results from autoimmune β-cell destruction and requires lifelong insulin therapy. This study aimed to evaluate the safety and preliminary efficacy of intravenous allogeneic adipose-derived mesenchymal stem cells (MSCs, GXIPC1) in children with recent-onset T1DM.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this single-arm, open-label phase 1 trial, ten children (aged\u0026thinsp;\u0026ge;\u0026thinsp;5 years) diagnosed with T1DM within the previous 12 months received a single intravenous infusion of GXIPC1 at a dose of 1\u0026times;10⁶ cells/kg. The primary endpoint was safety over 6 months. Secondary endpoints included changes in HbA1c, fasting glucose, C-peptide, and daily insulin requirements at 1, 3, and 6 months after infusion.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eNo treatment-related serious adverse events occurred. Six participants experienced eight mild-to-moderate adverse events (mainly mild hypoglycemia managed by insulin adjustment), none related to GXIPC1. Vital signs and laboratory parameters remained stable. Median fasting glucose decreased from 15.3 mmol/L at baseline to 5.8 mmol/L at 1 month. Daily insulin requirements decreased by 44% at 3 months (median 22.5 to 12.5 IU/day), and one participant achieved insulin independence between months 3 and 6. Median HbA1c remained stable at 3 months (7.41%) and increased slightly at 6 months (8.27%), with 30% of participants showing values below baseline and 20% below 7.5%. C-peptide levels remained stable, suggesting preserved endogenous β-cell function.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIntravenous GXIPC1 was safe and well tolerated in children with recent-onset T1DM and demonstrated encouraging signals of improved glycemic control and reduced insulin dependence. Further evaluation in randomized phase 2 trials is warranted.\u003c/p\u003e","manuscriptTitle":"Safety and Preliminary Efficacy of Intravenous Allogeneic Adipose-Derived Mesenchymal Stem Cells (GXIPC1) in Patients with Type 1 Diabetes Mellitus: A Phase 1, Single-Arm, Open-Label Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 10:42:36","doi":"10.21203/rs.3.rs-8189178/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":"fff427c4-5a86-4f76-a64a-81285e6f74b2","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-10T18:39:18+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-16 10:42:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8189178","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8189178","identity":"rs-8189178","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}