Safwan M, Bourgleh MS, Baroudi L, Almsned A, AlBalawi R, Aibour B, AlFawaz S, Bourgleh SM, Haider KH. Entering the era of living biopharmaceuticals for treating knee osteoarthritis: A systematic review and network meta-analysis. World J Stem Cells 2025; 17(8): 107076 [DOI: 10.4252/wjsc.v17.i8.107076]
Corresponding Author of This Article
Khawaja Husnain Haider, PhD, Professor, Department of Basic Sciences, Sulaiman Al Rajhi University, PO Box 777, Al Bukairiyah 51941, AlQaseem, Saudi Arabia. khhaider@gmail.com
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
Meta-Analysis
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Moaz Safwan, Mariam Safwan Bourgleh, Lubabah Baroudi, Aseel Almsned, Rawan AlBalawi, Batoul Aibour, Shahad AlFawaz, Khawaja Husnain Haider, Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, AlQaseem, Saudi Arabia
Safwan M Bourgleh, Department of Orthopedic Surgery, Hotat Sudair General Hospital, Second Health Cluster, Riyadh 15333, Saudi Arabia
Co-first authors: Moaz Safwan and Mariam Safwan Bourgleh.
Author contributions: Safwan M and Bourgleh MS contributed equally to this study and are co-first authors of this manuscript; Baroudi L and AlBalawi R performed the full-text screening; Baroudi L, Almsned A, and Aibour B performed data extraction; Safwan M wrote the methodology and data analysis; Bourgleh MS registered the study protocol on the International Prospective Register of Systematic Reviews, performed database screening, reviewed data extraction and analysis, and wrote the introduction; Baroudi L participated in writing the results; Almsned A reviewed the screening of reports and quality assessment; AlBalawi R reviewed the data analysis; Aibour B performed the quality assessment; AlFawaz S reviewed the quality assessment, designed the study tables, and organized supplementary materials and references; Bourgleh SM reviewed the full text screening and data extraction, performed database analysis, and participated in writing the methodology and results sections; Haider KH designed the study protocol, assigned tasks, wrote the manuscript, modified the paper per the journal’s requirements, and submitted it for publication; All authors read and approved the final version of the manuscript.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised in accordance with the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Khawaja Husnain Haider, PhD, Professor, Department of Basic Sciences, Sulaiman Al Rajhi University, PO Box 777, Al Bukairiyah 51941, AlQaseem, Saudi Arabia. khhaider@gmail.com
Received: March 16, 2025 Revised: May 16, 2025 Accepted: July 2, 2025 Published online: August 26, 2025 Processing time: 159 Days and 21.8 Hours
Abstract
BACKGROUND
Knee osteoarthritis (KOA) is a leading cause of arthritis-related morbidity. Mesenchymal stem cells (MSCs), as living biopharmaceuticals, have emerged as a potential treatment option due to their anti-inflammatory and immunomodulatory properties.
AIM
To compare the safety and efficacy of allogenic MSCs (AlloMSCs) vs autologous MSCs (AutoMSCs) in treating KOA in clinical settings.
METHODS
We conducted a systematic review and network meta-analysis to compare the safety and efficacy of AlloMSCs vsAutoMSCs in treating KOA. Our systematic search of four databases, including PubMed, Cochrane, Embase, and ClinicalTrials.gov, identified relevant randomized controlled trials (RCTs) reporting MSC-based treatment for KOA and reporting visual analog scale, Western Ontario and McMaster Universities Osteoarthritis scores, and adverse events. We assessed the methodological quality of the studies using the Cochrane Collaboration tool and calculated risk ratios (RRs) and weighted mean differences [with 95% confidence intervals (CIs)]. Our statistical analyses used the R-Studio network meta-packages (version 2023.12.0). The study protocol was pre-registered on the International Prospective Register of Systematic Reviews (ID: CRD42024590866).
RESULTS
Nineteen RCTs involving 1216 patients with KOA met the inclusion criteria of the study. The network meta-analysis showed that AlloMSCs gave a significant reduction in visual analog scale scores by 14.91 points (95%CI: -24.52 to -5.30) vs 12.95 points with AutoMSCs (95%CI: -24.42 to -1.48). For Western Ontario and McMaster Universities Osteoarthritis score, AlloMSCs led to a significant reduction of 23.12 points (95%CI: -31.15 to -15.10) compared with 12.45 points using AutoMSCs (95%CI: -19.31 to -5.59), thus revealing a significant improvement with AlloMSCs (weighted mean difference: -10.62, 95%CI: -21.23 to -0.11). Additionally, AutoMSCs treatment showed a higher risk of joint-related adverse events (RR = 1.39, 95%CI: 1.07-1.79) compared with AlloMSCs (RR = 1.13, 95%CI: 1.01-1.25).
CONCLUSION
AlloMSCs may offer superior clinical outcomes with a lower risk of adverse events compared with AutoMSCs in the treatment of KOA. However, the need for further RCTs directly comparing the two MSC types is crucial to validate this data, underscoring the importance of our findings in this field.
Core Tip: Knee osteoarthritis (KOA) is the leading cause of arthritis-related morbidity. Mesenchymal stem cells (MSCs) are living biodrugs, offering a potential treatment option due to their anti-inflammatory and immunomodulatory properties. We compared the safety and efficacy of allogenic MSCs vs autologous MSCs in treating KOA in clinical settings, using published data from 19 randomized controlled trials that reported visual analog scale scores, Western Ontario and McMaster Universities Osteoarthritis scores, and adverse events. Our network meta-analysis data revealed that allogenic MSCs may offer superior clinical outcomes at a lower risk of adverse events than autologous MSCs in treating KOA.
