Allogeneic Umbilical Cord Mesenchymal Stromal Cells for Knee Osteoarthritis: Systematic Review and Meta-Analysis of Controlled Injection Trials

Background Knee osteoarthritis is a leading cause of chronic pain and reduced mobility worldwide. Intra-articular corticosteroids and hyaluronic acid injections are commonly used, but many patients experience limited durability of symptom improvement. Allogeneic umbilical cord derived mesenchymal stromal cells (UC-MSCs) have emerged as a regenerative medicine strategy intended to modulate inflammation and improve clinical outcomes. Objective To evaluate controlled clinical trial evidence for intra-articular allogeneic UC-MSC therapy in symptomatic knee osteoarthritis, with emphasis on durability of pain improvement at 12 months. Methods A systematic review was conducted to identify controlled clinical trials evaluating intra-articular allogeneic UC-MSCs for knee osteoarthritis with comparator injection arms. The primary endpoint was WOMAC pain at 12 months. Secondary outcomes included WOMAC total at 12 months. When trials did not provide numeric endpoint values in tables, values were extracted from published figures as estimated mean and dispersion measures. Outcomes were synthesized under a random effects framework with consideration of comparator type (hyaluronic acid vs corticosteroid). Results Two controlled trials met criteria for quantitative synthesis at 12 months. Across comparator subgroups, UC-MSC therapy demonstrated lower WOMAC pain scores at 12 months compared with control injections. UC-MSC therapy also demonstrated lower WOMAC total scores at 12 months relative to comparator injection arms. One phase I single-arm study was included in qualitative synthesis for feasibility and safety interpretation but was not eligible for pooled analysis. Conclusion Controlled clinical trial evidence suggests intra-articular allogeneic UC-MSC therapy may provide durable improvements in knee osteoarthritis pain at 12 months compared with standard injection-based comparators. Larger randomized trials with standardized reporting are needed to further define efficacy, durability, and safety across broader populations.