Mesenchymal stem cell-derived extracellular vesicles in joint diseases: Therapeutic effects and underlying mechanisms

Abstract

Joint diseases greatly impact the daily lives and occupational functioning of patients globally. However, conventional treatments for joint diseases have several limitations, such as unsatisfatory efficacy and side effects, necessitating the exploration of more efficacious therapeutic strategies. Mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have demonstrated high therapeutic efficacyin tissue repair and regeneration, with low immunogenicity and tumorigenicity. Recent studies have reported that EVs-based therapy has considerable therapeutic effects against joint diseases, including osteoarthritis, tendon and ligament injuries, femoral head osteonecrosis, and rheumatoid arthritis. Herein, we review the therapeutic potential of various types of MSC-EVs in the aforementioned joint diseases, summarise the mechanisms underlying specific biological effects of MSC-EVs, and discuss future prospects for basic research on MSC-EV-based therapeutic modalities and their clinical translation. In general, this review provides an in-depth understanding of the therapeutic effects of MSC-EVs in joint diseases, as well as the underlying mechanisms, which may be beneficial to the clinical translation of MSC-EV-based treatment. The translational potential of this article: MSC-EV-based cell-free therapy can effectively promote regeneration and tissue repair. When used to treat joint diseases, MSC-EVs have demonstrated desirable therapeutic effects in preclinical research. This review may supplement further research on MSC-EV-based treatment of joint diseases and its clinical translation.

Keywords: Extracellular vesicles; Mesenchymal stem cells; Osteoarthritis; Osteonecrosis of the femoral head; Rheumatoid arthritis; Tendon and ligament injuries.

Graphical abstract

Figure 1

MSCs origin and MSC-EXOs biogenesis. MSCs can be isolated from various sources, such as bone marrow, fat tissue, umbilical cord, and synovium. MSC-EXOs secretion involves multiple stages, such as endocytosis, early and late endosome formation, multivesicular body formation, and exocytosis. MSC-EXOs contents include proteins, RNAs, DNAs, amino acids, and metabolites.

Figure 2

MSC-EXOs in OA treatment. In OA, MSC-EXOs can inhibit chondrocyte degeneration, M1 macrophage polarisation, and synovial fibroblast proliferation and migration. ECM/GelMA/EXOs, ECM–gelatin methacrylate–exosome scaffold; ESCs, embryonic stem cells; HA-SH microgels, thiolated hyaluronic acid microgels; LIPUS, low-intensity pulsed ultrasound; PTH, parathyroid hormone; SMSCs, synovial MSCs.

Figure 3

MSC-EXOs in tendon and ligament injury treatment. MSC-EXOs can accelerate the repair of damaged tendons by regulating the functions of TDSC. MSC-EXOs can also increase TBH by promoting bone and fibrocartilage formation at the tendon–bone interface. INOP, iron oxide nanoparticles; p-HA, photopolymerisable hyaluronic acid; PDGFR, platelet-derived growth factor receptors; WBPU, waterborne polyurethane.

Figure 4

MSC-EXOs in ONFH treatment. Blood supply disruption and osteonecrosis are the main pathologic features of ONFH. MSC-EXOs can ameliorate ONFH by promoting angiogenesis and osteogenesis in damaged areas.

Figure 5

MSC-EXOs in RA treatment. RA pathogenesis is closely related to intraarticular immune inflammatory responses, including adaptive immunity with T and B cells, innate immunity with macrophages, and immune tissue responses involving synovial fibroblasts. MSC-EXOs can ameliorate RA through regulating the biological functions of different cells within the joint.