Clinical and Structural Outcomes of Platelet-Rich Plasma and Mesenchymal Stromal Cell Therapies for Knee Osteoarthritis: A Systematic Review

Background: Knee osteoarthritis is a highly prevalent degenerative condition, characterized by chronic pain, joint stiffness, and functional limitation, with a significant impact on quality of life. Conventional therapies have limited efficacy, especially in the moderate and advanced stages of the disease. In this context, biological therapies, such as platelet-rich plasma (PRP) and stromal stem cells, have been investigated as promising alternatives due to their immunomodulatory and regenerative potential. Objectives: To analyze the clinical, structural, and safety outcomes of platelet-rich plasma and mesenchymal stromal/stem cell-based therapies in adults with knee osteoarthritis. Methods: This is a systematic review registered in PROSPERO (CRD4202.51153170). Only randomized controlled trials were eligible involving adults with knee osteoarthritis treated with PRP and/or stromal stem cells, either alone or in combination, were included. The searches were conducted in the PubMed, Web of Science, Cochrane Library, Scopus, and Virtual Health Library databases. The assessment of the risk of bias was conducted using the RoB 2 tool, and the certainty of the evidence was analyzed using the GRADE system. Results: However, substantial heterogeneity in cell sources, doses, administration protocols, comparators, and follow-up periods limits direct comparisons and prevents the definition of a standardized therapeutic approach. The available evidence suggests potential clinical benefits of cellular therapies for knee osteoarthritis; however, substantial heterogeneity in cell sources, doses, administration protocols, comparators, and follow-up periods limits the ability to define a standardized therapeutic approach. Clinical improvements were reported across several stem cell-based protocols, although the magnitude and duration of these effects varied among studies. The structural effects on cartilage were variable, with limited evidence of consistent cartilage regeneration. Conclusions: PRP and stromal stem cells present relevant clinical benefits in the treatment of knee osteoarthritis, especially in pain reduction and functional improvement. PRP and mesenchymal stromal/stem cell-based therapies may provide improvements in pain and joint function in patients with knee osteoarthritis. However, the heterogeneity of cellular sources, treatment protocols, comparators, and follow-up periods limits direct comparisons and conclusions regarding superiority. Evidence regarding structural outcomes and long-term effects remains uncertain, supporting the need for further well-designed randomized controlled trials with standardized protocols and longer follow-up.