Abstract
BACKGROUND: This study focuses on addressing the challenges associated with temporomandibular joint osteoarthritis (TMJOA), a condition currently considered incurable. Osteoarthritis (OA) is a degenerative disease of cartilage and tissues that affects the temporomandibular joint (TMJ). The potential of interferon-γ (IFN-γ)-primed three-dimensional (3D) spheroids of umbilical cord-derived mesenchymal stem cells (UC-MSCs) was investigated as a therapeutic intervention for TMJOA. This research aims to confirm that enhanced 3D UC-MSC spheroids are more effective than their two-dimensional (2D) counterparts. METHODS: Effective conditions for IFN-γ-primed 3D spheroids in the treatment of temporomandibular joint osteoarthritis (TMJOA) were determined. The therapeutic potential was confirmed by co-culturing with synovium-derived cells from patients with temporomandibular disorder (TMD-SDCs). The therapeutic efficacy was confirmed by injecting IFN-γ-primed 3D spheroids into rats with TMJOA. RESULTS: Co-culturing TMD-SDCs with IFN-γ-primed 3D UC-MSC spheroids resulted in significantly improved regenerative and anti-inflammatory effects compared to co-cultures with 2D UC-MSCs. Validation in TMJOA rats further supported the promising effects of IFN-γ-primed 3D spheroids of UC-MSCs. The 3D spheroids group showed rapid recovery based on micro-computed tomography images, histology images, and pain response. CONCLUSION: MSCs were enhanced using cytokine priming and 3D spheroid culture. We successfully established the effective priming conditions for the therapeutic application of IFN-γ-primed 3D spheroids. The findings suggest their potential benefits in the treatment of TMJOA which is currently incurable and inform further advancements in regenerative medicine.