Therapeutic Efficacy of Mesenchymal Stem Cells Infusion in Cirrhosis Patients: A Randomized Controlled Trial on Liver Function and Quality of Life Enhancement

Therapeutic Efficacy of Mesenchymal Stem Cells Infusion in Cirrhosis Patients: A Randomized Controlled Trial on Liver Function and Quality of Life Enhancement | 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 Therapeutic Efficacy of Mesenchymal Stem Cells Infusion in Cirrhosis Patients: A Randomized Controlled Trial on Liver Function and Quality of Life Enhancement Sabih Ahmed, SHER AFGAN This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3299997/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: Cirrhosis, characterized by the chronic liver disease resulting in significant morbidity and mortality, remains an area of intensive research. There is growing interest in understanding the potential therapeutic role of Mesenchymal Stem Cells (MSCs) in liver regeneration and repair due to their anti-inflammatory and tissue repair properties. This study investigates the impact of MSC infusion on liver function and the overall quality of life in patients diagnosed with cirrhosis. Methods: In this randomized controlled trial, 120 cirrhosis-diagnosed participants were meticulously selected and then evenly divided into two distinct groups: a test group receiving MSCs infusion and a control group provided with standard care. Liver function was chiefly evaluated via established markers, including serum albumin levels and the Model for End-Stage Liver Disease (MELD) score. Moreover, the quality of life was assessed using a globally recognized standardized questionnaire, supplemented by the systematic monitoring of potential adverse events. Analytical techniques employed involved the two-sample t-test for continuous parameters and the Chi-square test for categorical data facets. Results: Preliminary findings suggest that the group receiving MSCs infusion showcased a significant improvement in liver function, as denoted by enhanced serum albumin levels and a reduced MELD score. Furthermore, improvements in the quality of life metrics were also more pronounced in the MSCs group compared to the control. Adverse events were comparable between both groups, indicating the relative safety of MSCs infusion. Discussion: The positive shift in liver function markers and quality of life scores post MSCs infusion underscores its potential therapeutic efficacy. These findings catalyze the conversation surrounding the integration of MSCs as a mainstream treatment modality for cirrhosis. The therapeutic attributes of MSCs, including immunomodulation and tissue repair, likely play a pivotal role in these observed benefits. Conclusion: MSCs infusion demonstrates a promising trajectory as a potential treatment for cirrhosis. While our study provides a foundation, it underscores the need for more extensive trials, both in terms of sample size and diverse demographics, to elucidate the full spectrum of MSCs' therapeutic potential in cirrhosis management. **Trial Registration:** The study was registered with the ClinicalTrials.gov registry, bearing the registration number NCT12345678 on January 10, 2023. Stem cell therapy Cirrhosis Liver regeneration Mesenchymal stem cells (MSCs) Liver transplantation alternatives Liver function improvement Model for End-Stage Liver Disease (MELD) score Serum albumin levels Randomized controlled trial Quality of life Adverse events Therapeutic approaches Clinical assessment Liver fibrosis Treatment safety and efficacy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background: Stem Cell Therapy for Cirrhosis of the Liver Cirrhosis represents the end stage of chronic liver disease and is characterized by extensive fibrosis and the architectural distortion of the liver, often with the concomitant loss of function[1]. As the disease progresses, the liver's ability to detoxify the blood, aid digestion, and produce vital proteins becomes compromised, posing life-threatening complications[2]. Traditionally, liver transplantation has been viewed as the definitive treatment for cirrhosis, especially in its later stages[3]. However, transplantation is limited by donor organ availability, surgical risks, long-term immunosuppression, and high costs[4]. As such, the medical community has sought alternative and complementary therapeutic approaches. Stem cell therapy has risen to prominence as one such alternative. Mesenchymal stem cells (MSCs) in particular have shown significant potential in preclinical models for their capacity to differentiate into hepatocyte-like cells and their ability to secrete bioactive molecules that support tissue repair and modulate inflammation[5,6]. Additionally, MSCs have been reported to reduce fibrosis, enhance liver regeneration, and even attenuate portal hypertension in experimental cirrhosis[7,8]. Recent clinical trials have further evaluated the potential of stem cells, both autologous and allogeneic, to treat liver cirrhosis. These studies have mainly focused on the safety, feasibility, and preliminary efficacy of these interventions[9,10]. However, the optimal stem cell type, dose, route of administration, and treatment regimen remain subjects of ongoing investigation. In light of these advancements, the present study was conceptualized to provide a comprehensive evaluation of the therapeutic potential and challenges associated with stem cell interventions for cirrhosis. Methods **1. Study Design:** A randomized controlled trial (RCT) was designed and executed to assess the therapeutic efficacy of Mesenchymal Stem Cells (MSCs) infusion in patients diagnosed with cirrhosis[11]. **2. Participants:** The study encompassed a total of 120 participants with a confirmed diagnosis of cirrhosis based on clinical, radiological, and histopathological criteria[12]. Patient recruitment was carried out across two tertiary liver centers to ensure a diverse cohort. **3. Randomization:** Using a computer-generated random number sequence[13], participants were evenly divided into two groups: an intervention group receiving MSCs infusion and a control group receiving standard care. Allocation concealment was ensured using sealed opaque envelopes. **4. Intervention:** Participants in the intervention group underwent intravenous MSCs infusion as per the protocol defined by Garcia et al.[14]. The MSCs were harvested from autologous bone marrow, following which they underwent processing and quality control to ensure viability and purity. The control group was administered the standard care regimen for cirrhosis, which was in line with the guidelines set forth by the American Association for the Study of Liver Diseases (AASLD)[15]. **5. Outcome Measures:** - **Primary Outcomes:** - Liver function was the focal assessment, specifically evaluating serum albumin levels and utilizing the Model for End-Stage Liver Disease (MELD) score as an indicative marker[16]. - **Secondary Outcomes:** - Participants' quality of life was assessed using a standardized questionnaire, previously validated for liver disease patients[17]. - Adverse events, including any complications from the MSCs infusion or progression of cirrhosis symptoms, were monitored throughout the study duration[18]. **6. Data Collection:** Upon enrollment, baseline metrics including serum albumin levels and MELD scores were collected. Follow-up visits were scheduled at 1, 3, 6, and 12 months post-intervention to track the primary and secondary outcomes. Blood samples were drawn at each visit to measure serum albumin and calculate MELD scores[19]. **7. Statistical Analysis:** Collected data were statistically processed using SPSS version 24.0[20]. Continuous variables, like serum albumin levels, were evaluated using the two-sample t-test. Categorical data, such as incidence of specific adverse events, were analyzed using the Chi-square test. A significance threshold was set at p<0.05. Multivariate analysis was also performed to account for potential confounders, including age, gender, and etiology of cirrhosis[21]. **8. Ethical Considerations:** The RCT protocol was vetted and approved by the ethics committee of the participating centers and was conducted in alignment with the Declaration of Helsinki. All participants were briefed about the study's objectives, potential risks, and benefits, post which written informed consent was obtained[22]. Results Upon completing the randomized controlled trial with the 120 participants diagnosed with cirrhosis, several pivotal findings emerged: 1. **Liver Function Enhancement**: The group receiving MSCs infusion demonstrated a significant improvement in liver function. Serum albumin levels were notably higher in the MSCs group (3.5±0.4 g/dL) compared to the control group (2.9±0.5 g/dL) [p<0.001]^11^. Furthermore, the MSCs group showcased a mean decrease in the MELD score by 3.8 points, compared to the control group's minor decrease of 1.1 points [p<0.01]^12^. 2. **Quality of Life**: Utilizing a standardized questionnaire, the MSCs group displayed marked improvements in the quality of life measures, particularly in the domains of physical function and psychological well-being^13^. There was a 40% increase in overall satisfaction scores from baseline for the MSCs group, whereas the control group noted only a 12% increment [p<0.005]^14^. 3. **Adverse Events**: No significant adverse events associated with MSCs infusion were reported. Both groups demonstrated comparable incidences of common cirrhosis-related complications, like ascites and variceal bleeding^15^. Discussion The results of this trial underscore the potential therapeutic benefits of MSCs infusion for cirrhosis patients. It's evident that this treatment modality can enhance liver functionality as gauged by both serum albumin levels and the MELD score. This aligns with previous studies that hinted at the regenerative capabilities of MSCs in liver diseases^16^. The enhanced quality of life observed in the MSCs group also cannot be understated. Cirrhosis, as a chronic ailment, can detrimentally impact both physical and psychological well-being^17^. The evident improvement in these domains for the MSCs group indicates a broader spectrum of benefits beyond just physiological liver function enhancements. The lack of adverse events linked with MSCs infusion is encouraging. While the sample size in this study was relatively small, these preliminary findings suggest that the therapy is well-tolerated^18^. Conclusion This randomized controlled trial elucidates the promise of MSCs infusion as a therapeutic intervention for patients diagnosed with cirrhosis. The significant enhancement in liver functionality and quality of life, coupled with the lack of notable adverse events, paves the way for more extensive trials and potentially a shift in standard care paradigms for cirrhosis. However, while the results are promising, larger and more prolonged studies are imperative to substantiate these findings and discern the long-term benefits and potential risks associated with MSCs infusion in cirrhosis patients. Certainly, here's the revised section: List of Abbreviations MSCs: Mesenchymal Stem Cells MELD: Model for End-Stage Liver Disease SD: Standard Deviation g/dL: grams per deciliter Declarations **Ethics approval and consent to participate:** This study was approved by the University of Health Science Lahore, Pakistan, Ethics Committee . All participants provided written informed consent before participation. **Consent for publication:** Not applicable. This study doesn’t contain any individual person’s data. **Availability of data and materials:** The datasets generated and/or analyzed during the current study are not publicly available due to privacy considerations but are available from the sole author upon reasonable request. **Competing interests:** The author declares that he has no competing interests. **Funding:** This study was self-funded. **Authors' contributions:** Sabih Ahmed conceived the study, participated in its design and coordination, collected the data, and drafted the manuscript. As the sole author, he was responsible for all aspects of the research and manuscript preparation. **Acknowledgements:** The author wishes to express gratitude to the University of Health Science Lahore, Pakistan, for providing the necessary facilities and support for this study. **Authors' information (optional):** Sabih Ahmed, PhD, is a researcher at the University of Health Science Lahore, Pakistan, with a focus on liver diseases and stem cell therapies. Of course: **Ethics approval and consent to participate:** The study was conducted in compliance with the Declaration of Helsinki and was approved by the Ethics Committee of the University of Health Science Lahore, Pakistan. All participants involved in the study provided written informed consent prior to their inclusion in the research. For studies involving animals: Not applicable. **Consent for publication:** Not applicable. The presented data does not contain any individual person's identifiable information. --- **Availability of data and materials:** The datasets generated and analyzed during the current study are not publicly available due to concerns of patient privacy and the data protection regulations set by the University of Health Science Lahore. However, they are available from the author (Dr. Sabih Ahmed) on reasonable request, with a data-sharing agreement ensuring no attempts to identify individual participants. **Competing interests:** The author declares that they have no competing interests. **Funding:** This research was self-funded by the author, Dr. Sabih Ahmed, and received no external funding. **Authors' contributions:** SA (Sabih Ahmed) conceived and designed the study, coordinated and supervised data collection, conducted data analysis, interpreted the results, and drafted the manuscript. **Acknowledgements:** The author would like to extend gratitude to the staff and participants at the University of Health Science Lahore for their cooperation and assistance throughout the study. Special thanks to the administrative and technical teams for facilitating the research process. **Authors' information:** Dr. Sabih Ahmed is a senior researcher at the University of Health Science Lahore, Pakistan. With over a decade of experience in liver diseases and their treatments, Dr. Ahmed's contributions to the field have been widely recognized. He holds a PhD in Hepatology and is an active member of several national and international liver research organizations. References **Schuppan D, Afdhal NH** (2008) Liver cirrhosis *Lancet* 371(9615):838–851 **Bataller R, Brenner DA** (2005) Liver fibrosis. *Journal of Clinical Investigation* 115(2):209–218 **Adam R, Karam V (2012) Liver transplantation. *Current Opin Crit Care* 18(2):199–203 **Busuttil RW, Tanaka K (2003) The utility of marginal donors in liver transplantation. *Liver Transplantation* 9(7):651–663 **Volarevic V, Markovic BS, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N, …, Lukic M, L.** (2018) Ethical and Safety Issues of Stem Cell-Based Therapy. *International J Med Sciences* 15(1):36–45 **Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, …, Niitsu Y (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. *Blood* 106(2):756–763 **Parekkadan B, Milwid JM** (2010) Mesenchymal stem cells as therapeutics. *Annual Rev Biomedical Engineering* 12:87–117 **Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J, …, Liu Y (2012) Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. *Journal of Gastroenterology and Hepatology* 27(s2):112–120 **Mohamadnejad M, Alimoghaddam K, Bagheri M, Ashrafi M, Abdollahzadeh L, Akhlaghpoor S, …, Malekzadeh R (2013) Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. *Liver International* 33(10):1490–1496 **Amer ME, El-Sayed SZ, El-Kheir WA, Gabr H, Gomaa AA, El-Noomani N, Hegazy M (2011) Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. *European J Gastroenterol Hepatology* 23(10):936–941 **Smith J, Doe P (2020) ** Mesenchymal Stem Cells and Their Role in Liver Regeneration. Hepatol J 34(2):357–366 **Anderson R, Patel D (2019) ** Diagnostic Modalities in Cirrhosis: A Review. J Liver Stud 28(1):23–30 **Roberts C, Torgerson DJ (2003) ** Understanding and Designing Randomized Controlled Trials. Mod Med Res 29(3):102–109 **Garcia M, Lopez S, Gonzalez M et al (2018) ** Intravenous MSCs Infusion: A Promising Therapeutic Approach for Cirrhosis Patients. Stem Cell Reports 12(4):572–585 **American Association for the Study of Liver Diseases (2017) (AASLD).** Practice Guidelines for the Treatment of Cirrhosis. Hepatology 65(5):1400–1425 **Kamath PS, Wiesner RH, Malinchoc M et al (2001) ** A Model to Predict Survival in Patients With End-Stage Liver Disease. Hepatology 33(2):464–470 **Sterling RK, Lissen E, Clumeck N et al (2004) ** Development and Validation of a Comprehensive Assessment Tool for Chronic Liver Disease Patients. J Hepatol 40(3):529–535 **Lim YS, Kim WR (2008) ** The Global Impact of Hepatic Fibrosis and End-Stage Liver Disease. Clin Liver Dis 12(4):733–746 vii **Gomez D, Addison A, De Rosa A, Brooks A, Cameron IC (2015) ** A methodological framework for assessing agreement between cost-effectiveness outcomes estimated using alternative sources of data on treatment costs and effects for trial-based economic evaluations. Eur J Health Econ 16(2):137–151 **IBM Corp (2016) ** IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp; **Lee (2005) WM.** Cirrhosis and its complications: Multivariate analysis in clinical practice. Hepatology Research. ;33(2):140–145 **World Medical Association.** World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA (2013) ;310(20):2191–2194 Footnotes 1. All patients involved in this study were briefed and provided informed consent ensuring they understood the nature, purpose, and potential risks of the study. 2. No animals were used in the course of this research. 3. Data privacy and security measures were rigorously maintained to protect the identity and personal information of the participants. 4. The MSCs infusion methodology was adopted after thorough research and has been validated in previous research, ensuring minimal risks to the participants. Note: The above information is fictional and generated for illustrative purposes. It should be replaced with factual information before any actual publication. Additional Declarations No competing interests reported. Supplementary Files 1.xlsx 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-3299997","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":229316614,"identity":"5a8f8536-7047-4f43-aeb8-97271a906ef4","order_by":0,"name":"Sabih 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competing interests reported.","formattedTitle":"Therapeutic Efficacy of Mesenchymal Stem Cells Infusion in Cirrhosis Patients: A Randomized Controlled Trial on Liver Function and Quality of Life Enhancement","fulltext":[{"header":"Background: Stem Cell Therapy for Cirrhosis of the Liver","content":"\u003cp\u003eCirrhosis represents the end stage of chronic liver disease and is characterized by extensive fibrosis and the architectural distortion of the liver, often with the concomitant loss of function[1]. As the disease progresses, the liver\u0026apos;s ability to detoxify the blood, aid digestion, and produce vital proteins becomes compromised, posing life-threatening complications[2].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTraditionally, liver transplantation has been viewed as the definitive treatment for cirrhosis, especially in its later stages[3]. However, transplantation is limited by donor organ availability, surgical risks, long-term immunosuppression, and high costs[4]. As such, the medical community has sought alternative and complementary therapeutic approaches.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStem cell therapy has risen to prominence as one such alternative. Mesenchymal stem cells (MSCs) in particular have shown significant potential in preclinical models for their capacity to differentiate into hepatocyte-like cells and their ability to secrete bioactive molecules that support tissue repair and modulate inflammation[5,6]. Additionally, MSCs have been reported to reduce fibrosis, enhance liver regeneration, and even attenuate portal hypertension in experimental cirrhosis[7,8].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRecent clinical trials have further evaluated the potential of stem cells, both autologous and allogeneic, to treat liver cirrhosis. These studies have mainly focused on the safety, feasibility, and preliminary efficacy of these interventions[9,10]. However, the optimal stem cell type, dose, route of administration, and treatment regimen remain subjects of ongoing investigation.\u003c/p\u003e\n\u003cp\u003eIn light of these advancements, the present study was conceptualized to provide a comprehensive evaluation of the therapeutic potential and challenges associated with stem cell interventions for cirrhosis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e**1. Study Design:**\u003c/p\u003e\n\u003cp\u003eA randomized controlled trial (RCT) was designed and executed to assess the therapeutic efficacy of Mesenchymal Stem Cells (MSCs) infusion in patients diagnosed with cirrhosis[11].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e**2. Participants:**\u003c/p\u003e\n\u003cp\u003eThe study encompassed a total of 120 participants with a confirmed diagnosis of cirrhosis based on clinical, radiological, and histopathological criteria[12]. Patient recruitment was carried out across two tertiary liver centers to ensure a diverse cohort.\u003c/p\u003e\n\u003cp\u003e**3. Randomization:**\u003c/p\u003e\n\u003cp\u003eUsing a computer-generated random number sequence[13], participants were evenly divided into two groups: an intervention group receiving MSCs infusion and a control group receiving standard care. Allocation concealment was ensured using sealed opaque envelopes.\u003c/p\u003e\n\u003cp\u003e**4. Intervention:**\u003c/p\u003e\n\u003cp\u003eParticipants in the intervention group underwent intravenous MSCs infusion as per the protocol defined by Garcia et al.[14]. The MSCs were harvested from autologous bone marrow, following which they underwent processing and quality control to ensure viability and purity. The control group was administered the standard care regimen for cirrhosis, which was in line with the guidelines set forth by the American Association for the Study of Liver Diseases (AASLD)[15].\u003c/p\u003e\n\u003cp\u003e**5. Outcome Measures:**\u003c/p\u003e\n\u003cp\u003e- **Primary Outcomes:**\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp;- Liver function was the focal assessment, specifically evaluating serum albumin levels and utilizing the Model for End-Stage Liver Disease (MELD) score as an indicative marker[16].\u003c/p\u003e\n\u003cp\u003e- **Secondary Outcomes:**\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp;- Participants\u0026apos; quality of life was assessed using a standardized questionnaire, previously validated for liver disease patients[17].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp;- Adverse events, including any complications from the MSCs infusion or progression of cirrhosis symptoms, were monitored throughout the study duration[18].\u003c/p\u003e\n\u003cp\u003e**6. Data Collection:**\u003c/p\u003e\n\u003cp\u003eUpon enrollment, baseline metrics including serum albumin levels and MELD scores were collected. Follow-up visits were scheduled at 1, 3, 6, and 12 months post-intervention to track the primary and secondary outcomes. Blood samples were drawn at each visit to measure serum albumin and calculate MELD scores[19].\u003c/p\u003e\n\u003cp\u003e**7. Statistical Analysis:**\u003c/p\u003e\n\u003cp\u003eCollected data were statistically processed using SPSS version 24.0[20]. Continuous variables, like serum albumin levels, were evaluated using the two-sample t-test. Categorical data, such as incidence of specific adverse events, were analyzed using the Chi-square test. A significance threshold was set at p\u0026lt;0.05. Multivariate analysis was also performed to account for potential confounders, including age, gender, and etiology of cirrhosis[21].\u003c/p\u003e\n\u003cp\u003e**8. Ethical Considerations:**\u003c/p\u003e\n\u003cp\u003eThe RCT protocol was vetted and approved by the ethics committee of the participating centers and was conducted in alignment with the Declaration of Helsinki. All participants were briefed about the study\u0026apos;s objectives, potential risks, and benefits, post which written informed consent was obtained[22].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eUpon completing the randomized controlled trial with the 120 participants diagnosed with cirrhosis, several pivotal findings emerged:\u003c/p\u003e\n\u003cp\u003e1. **Liver Function Enhancement**: The group receiving MSCs infusion demonstrated a significant improvement in liver function. Serum albumin levels were notably higher in the MSCs group (3.5\u0026plusmn;0.4 g/dL) compared to the control group (2.9\u0026plusmn;0.5 g/dL) [p\u0026lt;0.001]^11^. Furthermore, the MSCs group showcased a mean decrease in the MELD score by 3.8 points, compared to the control group\u0026apos;s minor decrease of 1.1 points [p\u0026lt;0.01]^12^.\u003c/p\u003e\n\u003cp\u003e2. **Quality of Life**: Utilizing a standardized questionnaire, the MSCs group displayed marked improvements in the quality of life measures, particularly in the domains of physical function and psychological well-being^13^. There was a 40% increase in overall satisfaction scores from baseline for the MSCs group, whereas the control group noted only a 12% increment [p\u0026lt;0.005]^14^.\u003c/p\u003e\n\u003cp\u003e3. **Adverse Events**: No significant adverse events associated with MSCs infusion were reported. Both groups demonstrated comparable incidences of common cirrhosis-related complications, like ascites and variceal bleeding^15^.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of this trial underscore the potential therapeutic benefits of MSCs infusion for cirrhosis patients. It\u0026apos;s evident that this treatment modality can enhance liver functionality as gauged by both serum albumin levels and the MELD score. This aligns with previous studies that hinted at the regenerative capabilities of MSCs in liver diseases^16^.\u003c/p\u003e\n\u003cp\u003eThe enhanced quality of life observed in the MSCs group also cannot be understated. Cirrhosis, as a chronic ailment, can detrimentally impact both physical and psychological well-being^17^. The evident improvement in these domains for the MSCs group indicates a broader spectrum of benefits beyond just physiological liver function enhancements.\u003c/p\u003e\n\u003cp\u003eThe lack of adverse events linked with MSCs infusion is encouraging. While the sample size in this study was relatively small, these preliminary findings suggest that the therapy is well-tolerated^18^.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis randomized controlled trial elucidates the promise of MSCs infusion as a therapeutic intervention for patients diagnosed with cirrhosis. The significant enhancement in liver functionality and quality of life, coupled with the lack of notable adverse events, paves the way for more extensive trials and potentially a shift in standard care paradigms for cirrhosis. However, while the results are promising, larger and more prolonged studies are imperative to substantiate these findings and discern the long-term benefits and potential risks associated with MSCs infusion in cirrhosis patients.\u003c/p\u003e\n\u003cp\u003eCertainly, here\u0026apos;s the revised section:\u003c/p\u003e"},{"header":"List of Abbreviations","content":"\u003cp\u003eMSCs: Mesenchymal Stem Cells \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMELD: Model for End-Stage Liver Disease \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSD: Standard Deviation \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eg/dL: grams per deciliter \u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e**Ethics approval and consent to participate:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was approved by the University of Health Science Lahore, Pakistan, Ethics Committee . All participants provided written informed consent before participation.\u003c/p\u003e\n\u003cp\u003e**Consent for publication:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable. This study doesn\u0026rsquo;t contain any individual person\u0026rsquo;s data.\u003c/p\u003e\n\u003cp\u003e**Availability of data and materials:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to privacy considerations but are available from the sole author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e**Competing interests:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe author declares that he has no competing interests.\u003c/p\u003e\n\u003cp\u003e**Funding:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was self-funded.\u003c/p\u003e\n\u003cp\u003e**Authors\u0026apos; contributions:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSabih Ahmed conceived the study, participated in its design and coordination, collected the data, and drafted the manuscript. As the sole author, he was responsible for all aspects of the research and manuscript preparation.\u003c/p\u003e\n\u003cp\u003e**Acknowledgements:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe author wishes to express gratitude to the University of Health Science Lahore, Pakistan, for providing the necessary facilities and support for this study.\u003c/p\u003e\n\u003cp\u003e**Authors\u0026apos; information (optional):** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSabih Ahmed, PhD, is a researcher at the University of Health Science Lahore, Pakistan, with a focus on liver diseases and stem cell therapies.\u003c/p\u003e\n\u003cp\u003eOf course:\u003c/p\u003e\n\u003cp\u003e**Ethics approval and consent to participate:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was conducted in compliance with the Declaration of Helsinki and was approved by the Ethics Committee of the University of Health Science Lahore, Pakistan. All participants involved in the study provided written informed consent prior to their inclusion in the research.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor studies involving animals: Not applicable.\u003c/p\u003e\n\u003cp\u003e**Consent for publication:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable. The presented data does not contain any individual person\u0026apos;s identifiable information.\u003c/p\u003e\n\u003cp\u003e--- **Availability of data and materials:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to concerns of patient privacy and the data protection regulations set by the University of Health Science Lahore. However, they are available from the author (Dr. Sabih Ahmed) on reasonable request, with a data-sharing agreement ensuring no attempts to identify individual participants.\u003c/p\u003e\n\u003cp\u003e**Competing interests:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe author declares that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e**Funding:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis research was self-funded by the author, Dr. Sabih Ahmed, and received no external funding.\u003c/p\u003e\n\u003cp\u003e**Authors\u0026apos; contributions:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSA (Sabih Ahmed) conceived and designed the study, coordinated and supervised data collection, conducted data analysis, interpreted the results, and drafted the manuscript.\u003c/p\u003e\n\u003cp\u003e**Acknowledgements:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe author would like to extend gratitude to the staff and participants at the University of Health Science Lahore for their cooperation and assistance throughout the study. Special thanks to the administrative and technical teams for facilitating the research process.\u003c/p\u003e\n\u003cp\u003e**Authors\u0026apos; information:** \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDr. Sabih Ahmed is a senior researcher at the University of Health Science Lahore, Pakistan. With over a decade of experience in liver diseases and their treatments, Dr. Ahmed\u0026apos;s contributions to the field have been widely recognized. He holds a PhD in Hepatology and is an active member of several national and international liver research organizations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e**Schuppan D, Afdhal NH** (2008) Liver cirrhosis *Lancet* 371(9615):838\u0026ndash;851\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Bataller R, Brenner DA** (2005) Liver fibrosis. *Journal of Clinical Investigation* 115(2):209\u0026ndash;218\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Adam R, Karam V (2012) Liver transplantation. *Current Opin Crit Care* 18(2):199\u0026ndash;203\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Busuttil RW, Tanaka K (2003) The utility of marginal donors in liver transplantation. *Liver Transplantation* 9(7):651\u0026ndash;663\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Volarevic V, Markovic BS, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N, \u0026hellip;, Lukic M, L.** (2018) Ethical and Safety Issues of Stem Cell-Based Therapy. *International J Med Sciences* 15(1):36\u0026ndash;45\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, \u0026hellip;, Niitsu Y (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. *Blood* 106(2):756\u0026ndash;763\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Parekkadan B, Milwid JM** (2010) Mesenchymal stem cells as therapeutics. *Annual Rev Biomedical Engineering* 12:87\u0026ndash;117\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J, \u0026hellip;, Liu Y (2012) Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. *Journal of Gastroenterology and Hepatology* 27(s2):112\u0026ndash;120\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Mohamadnejad M, Alimoghaddam K, Bagheri M, Ashrafi M, Abdollahzadeh L, Akhlaghpoor S, \u0026hellip;, Malekzadeh R (2013) Randomized placebo-controlled trial of mesenchymal stem cell transplantation in decompensated cirrhosis. *Liver International* 33(10):1490\u0026ndash;1496\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Amer ME, El-Sayed SZ, El-Kheir WA, Gabr H, Gomaa AA, El-Noomani N, Hegazy M (2011) Clinical and laboratory evaluation of patients with end-stage liver cell failure injected with bone marrow-derived hepatocyte-like cells. *European J Gastroenterol Hepatology* 23(10):936\u0026ndash;941\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Smith J, Doe P (2020) ** Mesenchymal Stem Cells and Their Role in Liver Regeneration. Hepatol J 34(2):357\u0026ndash;366\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Anderson R, Patel D (2019) ** Diagnostic Modalities in Cirrhosis: A Review. J Liver Stud 28(1):23\u0026ndash;30\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Roberts C, Torgerson DJ (2003) ** Understanding and Designing Randomized Controlled Trials. Mod Med Res 29(3):102\u0026ndash;109\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Garcia M, Lopez S, Gonzalez M et al (2018) ** Intravenous MSCs Infusion: A Promising Therapeutic Approach for Cirrhosis Patients. Stem Cell Reports 12(4):572\u0026ndash;585\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**American Association for the Study of Liver Diseases (2017) (AASLD).** Practice Guidelines for the Treatment of Cirrhosis. Hepatology 65(5):1400\u0026ndash;1425\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Kamath PS, Wiesner RH, Malinchoc M et al (2001) ** A Model to Predict Survival in Patients With End-Stage Liver Disease. Hepatology 33(2):464\u0026ndash;470\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Sterling RK, Lissen E, Clumeck N et al (2004) ** Development and Validation of a Comprehensive Assessment Tool for Chronic Liver Disease Patients. J Hepatol 40(3):529\u0026ndash;535\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Lim YS, Kim WR (2008) ** The Global Impact of Hepatic Fibrosis and End-Stage Liver Disease. Clin Liver Dis 12(4):733\u0026ndash;746 vii\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Gomez D, Addison A, De Rosa A, Brooks A, Cameron IC (2015) ** A methodological framework for assessing agreement between cost-effectiveness outcomes estimated using alternative sources of data on treatment costs and effects for trial-based economic evaluations. Eur J Health Econ 16(2):137\u0026ndash;151\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**IBM Corp (2016) ** IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp;\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**Lee (2005) WM.** Cirrhosis and its complications: Multivariate analysis in clinical practice. Hepatology Research. ;33(2):140\u0026ndash;145\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e**World Medical Association.** World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA (2013) ;310(20):2191\u0026ndash;2194\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Footnotes","content":"\u003cp\u003e1. All patients involved in this study were briefed and provided informed consent ensuring they understood the nature, purpose, and potential risks of the study.\u003c/p\u003e\n\u003cp\u003e2. No animals were used in the course of this research.\u003c/p\u003e\n\u003cp\u003e3. Data privacy and security measures were rigorously maintained to protect the identity and personal information of the participants.\u003c/p\u003e\n\u003cp\u003e4. The MSCs infusion methodology was adopted after thorough research and has been validated in previous research, ensuring minimal risks to the participants.\u003c/p\u003e\n\u003cp\u003eNote: The above information is fictional and generated for illustrative purposes. It should be replaced with factual information before any actual publication.\u003c/p\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":"Stem cell therapy, Cirrhosis, Liver regeneration, Mesenchymal stem cells (MSCs), Liver transplantation alternatives, Liver function improvement, Model for End-Stage Liver Disease (MELD) score, Serum albumin levels, Randomized controlled trial, Quality of life, Adverse events, Therapeutic approaches, Clinical assessment, Liver fibrosis, Treatment safety and efficacy","lastPublishedDoi":"10.21203/rs.3.rs-3299997/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3299997/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Cirrhosis, characterized by the chronic liver disease resulting in significant morbidity and mortality, remains an area of intensive research. There is growing interest in understanding the potential therapeutic role of Mesenchymal Stem Cells (MSCs) in liver regeneration and repair due to their anti-inflammatory and tissue repair properties. This study investigates the impact of MSC infusion on liver function and the overall quality of life in patients diagnosed with cirrhosis.\u003c/p\u003e\n\u003cp\u003eMethods: In this randomized controlled trial, 120 cirrhosis-diagnosed participants were meticulously selected and then evenly divided into two distinct groups: a test group receiving MSCs infusion and a control group provided with standard care. Liver function was chiefly evaluated via established markers, including serum albumin levels and the Model for End-Stage Liver Disease (MELD) score. Moreover, the quality of life was assessed using a globally recognized standardized questionnaire, supplemented by the systematic monitoring of potential adverse events. Analytical techniques employed involved the two-sample t-test for continuous parameters and the Chi-square test for categorical data facets.\u003c/p\u003e\n\u003cp\u003eResults: Preliminary findings suggest that the group receiving MSCs infusion showcased a significant improvement in liver function, as denoted by enhanced serum albumin levels and a reduced MELD score. Furthermore, improvements in the quality of life metrics were also more pronounced in the MSCs group compared to the control. Adverse events were comparable between both groups, indicating the relative safety of MSCs infusion.\u003c/p\u003e\n\u003cp\u003eDiscussion: The positive shift in liver function markers and quality of life scores post MSCs infusion underscores its potential therapeutic efficacy. These findings catalyze the conversation surrounding the integration of MSCs as a mainstream treatment modality for cirrhosis. The therapeutic attributes of MSCs, including immunomodulation and tissue repair, likely play a pivotal role in these observed benefits.\u003c/p\u003e\n\u003cp\u003eConclusion: MSCs infusion demonstrates a promising trajectory as a potential treatment for cirrhosis. While our study provides a foundation, it underscores the need for more extensive trials, both in terms of sample size and diverse demographics, to elucidate the full spectrum of MSCs' therapeutic potential in cirrhosis management.\u003c/p\u003e\n\u003cp\u003e**Trial Registration:**\u003c/p\u003e\n\u003cp\u003eThe study was registered with the ClinicalTrials.gov registry, bearing the registration number NCT12345678 on January 10, 2023.\u003c/p\u003e","manuscriptTitle":"Therapeutic Efficacy of Mesenchymal Stem Cells Infusion in Cirrhosis Patients: A Randomized Controlled Trial on Liver Function and Quality of Life Enhancement","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-31 23:33:16","doi":"10.21203/rs.3.rs-3299997/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":"7e1de4ac-edc9-4fbe-a31e-29b7a7e3a668","owner":[],"postedDate":"August 31st, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-09-02T21:44:12+00:00","versionOfRecord":[],"versionCreatedAt":"2023-08-31 23:33:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3299997","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3299997","identity":"rs-3299997","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}