Year 2

The long-term goal of this proposal is to develop stem cell-based treatment for major defects in the orofacial regions. Bisphosphonate related osteonecrosis of the jaw (BRONJ) is a recently described adverse side effect of bisphosphonate therapy, with an estimated 94% of cases reported in the oncologic patients receiving intravenous nitrogen-containing bisphosphonates (BP). Due to the lack of a testable animal model and limited biological tissue specimens, to date, the patho-physiological mechanisms underlying BRONJ remain largely unknown. We have successfully established BRONJ minipig and mouse models treated with oncologic doses of zolendronate (Zometa)/Dexamethasone (Dex) developed BRONJ-like pathological lesions with similar clinical, radiographic, and histological features as described in the human disease. These models will be used to understand mechanism of BRONJ and find appropriate therapeutic approaches for BRONJ.
We isolated a new population of stem cells from human orofacial tissue gingiva, a tissue source easily accessible from the oral cavity, namely GMSC, which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSC were capable of immunomodulatory functions. Cell-based therapy using systemic infusion of GMSC in experimental colitis significantly ameliorated both clinical and histopathological severity of the colonic inflammation, restored the injured gastrointestinal mucosal tissues, reversed diarrhea and weight loss, and suppressed the overall disease activity in mice. The therapeutic effect of hGMSC was mediated, in part, by the suppression of inflammatory infiltrates and inflammatory cytokines/mediators at the colonic sites. GMSC can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases.
In collaboration with investigators in Taiwan, we implanted one type of autologous OMSCs (periodontal ligament progenitors, PDLPs) to treat an orofacial infectious bone defect disease periodontitis. We examined the clinical outcome of three autologous PDLP-treated patients in an effort to provide primary knowledge on the effectiveness of this treatment approach and preliminary clinical evidence for randomized controlled trial in the future. Clinical examination indicated that local implantation of PDLPs may provide therapeutic benefit for the periodontal defects. All treated patients showed no adverse effects during the entire course of follow up. This study demonstrated clinical and experimental evidences supporting a potential efficacy and safety of utilizing autologous PDL cells in the treatment of human periodontitis.