Regenerative Therapy in Osteoarthritis Using Umbilical Cord-Origin Mesenchymal Stem Cells: A Critical Appraisal of...

Recent decades have witnessed a high prevalence of knee osteoarthritis among adults, which is associated with chronic pain, functional limitations, and decreased quality of life. Given the ineffectiveness of conventional cartilage regeneration approaches, umbilical cord-derived mesenchymal stem cells (UC-MSCs) have emerged as a potential regenerative therapy. In this study, it was aimed to determine whether UC-MSC treatment for knee osteoarthritis is effective, safe, and what is the optimal dosage to achieve optimal outcomes.

This study was conducted as a systematic review and meta-analysis based on the PRISMA 2020 guideline. The dose of cells was divided into four groups: less than 25 × 10⁶ (low), 25-50 × 10⁶ (medium), more than 50 × 10⁶ (high), and cases with no dose reported. An extensive search was conducted in PubMed, Embase, Scopus, Web of Science, ClinicalTrials.gov, and other sources up to September 2025. Randomized, phase I/II, and quasi-experimental clinical trial studies that used UC-MSCs in human patients with osteoarthritis were included in the analysis. Cochrane RoB and ROBINS-I tools were used to assess the quality of studies, and statistical analysis was performed using RevMan 5.4.

Of the 1427 identified articles, 8 studies with a total of 688 participants were finally included in the systematic review and meta-analysis. Although the analysis indicated that intra-articular injections of UC-MSCs reduced pain intensity (visual analog scale [VAS]) at both 6 months (standardized mean difference [SMD]: -0.86; 95% CI: -2.41 to 0.69; p=0.28) and 12 months (SMD: -1.02; 95% CI: -2.62 to 0.58; p=0.21), the observed reductions were not statistically significant. Notably, a subgroup analysis revealed that administration of a low-dose UC-MSC formulation resulted in a statistically significant reduction in pain scores at both 6 and 12 months (p ≤ 0.0001). In addition, there was also an improvement in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 6 months (SMD: -25.81; 95% CI: -45.15 to -6.46; p=0.009) compared to control. Compared to high-dose groups or control interventions (e.g., hyaluronic acid or placebo), low and medium doses (less than 25 × 10⁶ and 25-50 × 10⁶ million cells) demonstrated a superior efficacy. No serious treatment-related adverse events were reported, and the adverse events were mild, transient, and manageable.

UC-MSC treatment in patients with knee osteoarthritis is a safe and effective method for improving pain and motor function, and it represents a promising alternative to traditional treatments. Given the promising results of this study, further prospective studies with a standardized design and economic evaluations are recommended to enable wider clinical application of this method.