The goal 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 orofacial bone regeneration in large animal model,
• We identified that Erk1/2 signaling regulate both MSC-mediated bone regeneration and immunomodulation (manuscript in preparation).
• We showed that MSC-based immunotherapy involves in coupling via FasL/Fas to induce T cell apoptosis (Akiyama et al., Cell Stem Cell 2012).
• We have established jaw osteoradionecrosis (ORN) pre-clinical model and shown that mesenchymal stem cell-based implantation can cure ORN in minipigs (Xu et al., Cell Transplantation 2012).
• 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 (Patel et al., Oral Diseases 2012).