Background: Stem cell therapy is emerging as a potential treatment of osteoarthritis (OA) and chondral defects (CDs). However, there is a great deal of heterogeneity in the literature. The indications for stem cell use, the ideal tissue source, and the preferred outcome measures for stem cell-based treatments have yet to be determined.

Purpose: To provide clinicians with a comprehensive overview of the entire body of the current human literature investigating the safety and efficacy of intra-articular mesenchymal stem cell (MSC) therapy in all joints.

Methods: To provide a comprehensive overview of the current literature, all clinical studies investigating the safety and efficacy of intra-articular MSC therapy were included. PubMed, MEDLINE, and Cochrane Library databases were searched for published human clinical trials involving the use of MSCs for the treatment of OA and CDs in all joints. A total of 3867 publications were screened.

Results: Twenty-eight studies met the criteria to be included in this review. Fourteen studies treating osteoarthritis and 14 studies treating focal chondral defects were included. MSCs originating from bone marrow (13), adipose tissue (12), synovial tissue (2), or peripheral blood (2) were administered to 584 distinct individuals. MSCs were administered into the knee (523 knees), foot/ankle (61), and hip (5). The mean follow-up time was 24.4 months after MSC therapy. All studies reported improvement from baseline in at least 1 clinical outcome measure, and no study reported major adverse events attributable to MSC therapy.

Discussion: The studies included in this review suggest that intra-articular MSC therapy is safe. While clinical and, in some cases, radiological improvements were reported for both OA and CD trials, the overall quality of the literature was poor, and heterogeneity and lack of reproducibility limit firm conclusions regarding the efficacy of these treatments.

Conclusion: This review provides strong evidence that autologous intra-articular MSC therapy is safe, with generally positive clinical outcomes.