SHBC1664

T.SNG¹, K. TEO¹, S. ZHANG¹, A. LIM¹, R. WONG¹, S. LIM², W. S. TOH¹

National University of Singapore¹, Agency for Science, Technology and Research, Singapore(A*STAR)²

To investigate the immunomodulatory effects of mesenchymal stromal/stem cell (MSC) exosomes on repair and pain recovery in a rat model of temporomandibular joint osteoarthritis (TMJ-OA).

Twenty-eight rats were randomly divided into OA+Exo, OA+PBS, sham and naïve groups. Two weeks after OA induction by mono-iodoacetate, OA+Exo rats received intra-articular MSC exosome injections whereas OA+PBS rats received phosphate-buffered saline (PBS) at days 0, 7 and 14. Sham rats received needle pricks while naïve rats served as healthy controls. Pain response by head withdrawal threshold (HWT) of the rats was measured weekly. Transcriptomic and histological analysis were performed at 1 and 8 weeks respectively. The immunomodulatory and anti-nociceptive effects of MSC exosomes on macrophage polarization and chondrocyte release of nociceptive mediators were examined via macrophage and chondrocyte cultures.

At 8 weeks, OA+Exo rats showed pain recovery with significantly improved HWT. Relative to OA+PBS rats, OA+Exo rats showed reduced synovium inflammation and enhanced joint restoration. Early transcriptional profiling of the TMJ condyles revealed enhanced expression of M2 macrophage-associated genes and suppression of M1 macrophage-associated genes with exosome treatment. Consistently in macrophage cultures, MSC exosomes enhanced M2 over M1 polarization. In chondrocyte cultures, MSC exosomes reversed IL-1β-induced expression of nociceptive mediators and suppression of matrix synthesis.

Our results show that MSC exosomes modulated inflammation through enhanced M2 over M1 macrophage polarization to promote TMJ repair and pain recovery. This study provides the basis for further investigation of human MSC exosomes as a cell-free therapeutic for management of TMJ-OA in patients.