Intra-articular injection of exosomes derived from different stem cells in animal models of osteoarthritis: a systematic review and meta- analysis

Background: In recent years, the increasing incidence of osteoarthritis (OA) has attracted widespread public attention; however, the available effective treatments are limited. As a result, new therapeutic approaches, including stem cell and exosome therapies, have been proposed and are gradually gaining popularity. Because exosomes are immunocompatible, there is thought to be more potential for their use in clinical settings. This study summarizes the efficacy of exosomes in the treatment of OA.

Methods: In total, we conducted a comprehensive search of the PubMed, Web of Science, and Embase databases using medical subject headings terms to identify studies published from their inception until November 2023 that investigated the use of stem cell-derived exosomes in treating OA. We focused on specific outcomes including osteophyte score, chondrocyte count, pain level, qPCR and histological assessments such as the OARSI (Osteoarthritis research society international) score to measure cartilage degeneration. For data extraction, we used GetData Graph Digitizer to retrieve values from graphs, and the meta-analysis was conducted using RevMan 5.3 software. We chose mean difference (MD) as the primary effect measure since all included studies reported the same outcomes. Ultimately, 20 articles met the inclusion criteria and were included in the meta-analysis.

Results: We evaluated 20 studies comprising a total of 400 subjects. Compared with control groups, the exosome-treated groups showed significantly improved histological outcomes, as measured by the OARSI score (n = 400; MD = -3.54; 95% CI = [-4.30, -2.79]; P < 0.00001; I² = 98%). This indicates a marked reduction in cartilage degeneration and OA severity in the exosome-treated groups. Notably, exosome therapy was more effective when administered during the early stages of OA. Additionally, a once-weekly dosing schedule yielded better results compared to more frequent administrations. Of the three exosome isolation methods assessed, kit-based extraction demonstrated a trend toward superior therapeutic efficacy.

Conclusions: Exosome treatment improved OA compared to placebo treatment.