MSC exosomes alleviate pain and degeneration in A rat model of temporomandibular joint osteoarthritis

The efficacy of mesenchymal stem cell (MSC) therapies is increasingly attributed to paracrine secretion, particularly exosomes. Here, we investigate the effects of MSC exosomes on pain severity and cartilage degeneration in an experimental model of temporomandibular joint osteoarthritis (TMJ-OA). Exosomes were purified from human MSC conditioned medium. OA of bilateral TMJs was induced in rats by intra-articular injection of monosodium iodoacetate. Thereafter, weekly intra-articular injections of 100 µg of exosomes in 50µl of phosphate buffered saline (PBS) or equivalent volume of vehicle were given over 2, 4 and 8 weeks. Analyses were performed by head withdrawal threshold (HWT) measurement, micro-computed tomography, histology and immunohistochemistry, and Mankin scoring. Early gene expression changes induced by MSC exosomes were measured by transcriptomic analysis (using RT-PCR) of the condylar cartilage tissue. Comparison was made with OA rats that received PBS, as well as with sham and age-matched native rats. Our results showed that MSC exosomes attenuated the nociceptive response and reversed cartilage degradation and subchondral bone loss in rats with TMJ-OA. Exosome-treated lesions showed restoration of cartilage structure and subchondral bone integrity with improved Mankin scores, compared to PBS-treated lesions. Suppression of inflammation and oxidative damage in conjunction with enhanced cellular proliferation were observed. By 8 weeks, exosome-treated rats showed HWT recovery to a level similar to the sham rats, and displayed cartilage and subchondral bone restoration including appropriate condyle cartilage thickness, cellularity, matrix deposition, and subchondral bone architecture similar to that of sham control and closely resembled that of the native rats. Importantly, no adverse reactions were observed in all animals. Taken together, our findings demonstrate the efficacy of MSC exosomes to attenuate pain and reverse degeneration in an animal model of TMJ-OA. This study provides the basis for future use of human MSC exosomes as a ready-to-use and cell-free therapeutic for TMJ-OA.