Intra-articular MSC exosome-hyaluronic acid therapy alleviates TMJ-OA pain and degeneration

Objectives: To evaluate the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone in the treatment of temporomandibular joint osteoarthritis (TMJ-OA) in a rabbit model
Methods: MSC exosomes were prepared from an immortalized human MSC line. Nine rabbits (18 TMJs) were randomly assigned into three groups: (1) OA-HA, (2) OA-HA+Exo and (3) Sham. TMJ-OA was induced by intra-articular injection of mono-iodoacetate (MIA) in bilateral TMJs of 6 rabbits in OA-HA and OA-HA+Exo groups. Two weeks after OA induction, the rabbits received three weekly intra-articular injections of 50μl HA with 200μl phosphate-buffered saline (PBS) for the OA-HA group, or 50μl HA with 200μg exosomes in 200μl PBS for the OA-HA+Exo group. Rabbits in the sham group received only needle pricks. The effect of treatments on TMJ-OA pain was assessed weekly by measurements of the head withdrawal threshold (HWT) using an algometer. By the end of 8 weeks post-treatment, the rabbits were euthanized and the dissected TMJs were evaluated by micro-computed tomography (micro-CT) and histological assessment.
Results: OA-HA+Exo group showed gradual improvements in HWT, and the pain was reduced to baseline level of the sham animals as early as 4 weeks post-treatment. In contrast, OA-HA group showed minimal HWT improvement throughout the course of study. Notably, OA-HA+Exo group showed significantly better outcomes in the macroscopic score (P<0.05), OARSI histologic score (P<0.01) and synovial membrane inflammatory score (P<0.01) than that of OA-HA group, and were comparable to that of the sham group (P>0.05). As evidenced by micro-CT analysis, OA-HA+Exo group had a higher ratio of bone volume over total volume (BV/TV) than that of OA-HA group (P<0.01) and was comparable in BV/TV and trabecular thickness (Tb.Th) as the sham group (P>0.05).
Conclusions: This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 weekly intra-articular injections can suppress TMJ-OA inflammation and pain, while enhancing cartilage and subchondral bone repair, with significantly improved morphological and histological outcomes.