The purpose of this grant proposal is to characterize orofacial mesenchymal stem cells and determine the feasibility of reconstructing the orofacial defects caused by a variety of diseases such as osteonecrosis of the jaw using mesenchymal stem cells. Our study focuses on mesenchymal stem cell characterization, disease model generation, and mesenchymal stem cell-based tissue regeneration in small and large animal models,
• We identified that Erk1/2 respectively regulate MSC-based immunomodulation and osteogenic differentiation.
• We showed that MSC-based immunotherapy involves in coupling via FasL/Fas to induce T cell apoptosis.
• We have established jaw osteoradionecrosis (ORN) pre-clinical model and shown that mesenchymal stem cell-based implantation can cure ORN in minipigs.
• We continue to characterize effectiveness of mesenchymal stem cell-based therapy for bisphosphonate-associated osteonecrosis of the jaw (BRONJ) in pre-clinical model (manuscript in preparation) and confirmed some clinical phenotypes in BRONJ patients.
• We found that inflammation environment inhibits MSC-based bone formation via TNF Alpha and IFN-Gamma.