Platelet Rich Plasma and Mesenchymal Signalling Cell Therapy Reduce Pain and Improve Function: A Systematic Review and Meta Analysis of Randomized Controlled Trials with Meta Regression of Cell Count

Background and/or Objectives: Despite a plethora of research, low quality study designs and reporting have led to a lack of consensus on the efficacy of platelet-rich plasma (PRP) and mesenchymal signalling cell (MSC) therapy for the treatment of knee osteoarthritis (OA). An exhaustive synthesis of randomized controlled trials (RCT’s) was performed to provide an up to date analysis on the evidence for regenerative medicine and the impact of cell count on treatment.

Design: A systematic review and meta-analysis of randomized controlled trials with meta regression of cell count was performed according to PRISMA 2020 guidelines.

Setting : This review synthesized clinical studies.

Participants : Thirty-two unique papers were included; 21 for pain analysis (n=1182) and 19 for combined pain and function analysis (n=1034).

Interventions: Intraarticular injection of PRP versus MSC.

Main Outcome Measures: Pain and Function

Results: Statistically significant pain improvements at 6 months were observed in both PRP (p < 0.01, Cohen’s d = 2.2 [1.70, 2.71], I² = 93.7%) and MSC groups (p < 0.01, d = 2.10 [1.68, 2.51], I² = 10.0%). A significant difference between groups (p = 0.04, Q = 4.07) favored PRP. Combined pain and function analysis also showed significant improvement at 6 months for PRP (p < 0.01, d = 2.46 [1.55, 3.38], I² = 98.4%) and MSC (p < 0.01, d = 1.51 [0.80, 2.23], I² = 70.5%), but with no significant difference between groups (p = 0.11, Q = 2.59). Meta-regression showed no significant relationship (p > 0.05, R² ~0) between cell count and treatment effect in either subgroup.

Conclusions: This first known analysis of cell count and treatment effect in knee OA suggests cell dose does not influence outcomes. Both therapies, especially PRP, produced large improvements in pain and function. Future research should prioritize consistent cell count reporting and explore barriers to clinical adoption, as efficacy does not appear to be the limiting factor.