Regenerative Therapy in Osteoarthritis Using Umbilical Cord‐Origin Mesenchymal Stem Cells: A Critical Appraisal of Clinical Safety and Efficacy Through Systematic Review and Meta‐Analysis
Bibliographic record
Abstract
Introduction 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. Methods 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 × 10 6 (low), 25–50 × 10 6 (medium), more than 50 × 10 6 (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. Results 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 × 10 6 and 25–50 × 10 6 million cells) demonstrated a superior efficacy. No serious treatment‐related adverse events were reported, and the adverse events were mild, transient, and manageable. Conclusion 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".