REVERSAL OF MUCOSITIS BY GMSC-BASED THERAPY

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 美国南加州大学牙科学院颅面分子生物学中心 消化道粘膜炎（AT）是癌症治疗的一种使人衰弱的副作用，在接受化疗、骨髓移植和头颈部高剂量放疗的患者中，AT的比例很高。我们实验室最近的研究从人类牙龈中分离出一种新的干细胞群，即GMSC，它不仅表现出多能分化和自我更新能力，还具有明显的免疫调节功能。基于细胞的GMSC治疗显著改善了实验性小鼠结肠炎中结肠炎症的临床和组织病理学严重程度，推测是通过抑制炎性浸润，特别是白介素-17（IL-17）分泌细胞和无数炎性细胞因子/介质，并在结肠部位募集调节性T细胞（TCFs）。在另一种由化疗诱导的粘膜炎症的疾病模型中，我们观察到AT粘膜炎的显著逆转和体重的恢复，几乎100%的小鼠经历了GMSC的探索性单剂量治疗 实验方法：我们将研究GMSC对Treg和Th 17功能的免疫调节作用，以及它们如何通过体外和体内研究促进粘膜炎。光学相干断层扫描（OCT）与多光子显微镜（MMP）技术相结合，将用于破译干细胞归巢粘膜网站。我们将测试是否适应性转移与泛T细胞，离体扩增的T细胞，和药理学免疫增强疗法可以逆转粘膜损伤。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California Mucositis of the alimentary tract (AT) is a debilitating side effect of cancer therapies in a high percentage of patients receiving chemotherapy, bone marrow transplantation, and high-dose radiation to the head and neck.Recent studies from our laboratory have isolated a new population of stem cells from human gingiva, an easily accessible tissue source, namely GMSC, which exhibit not only multipotent differentiation and self-renewal capacities, but also possess distinct immunomodulatory functions. Cell-based therapy with GMSC significantly ameliorated both clinical and histopathological severities of the colonic inflammation in the experimental murine colitis, presumably by suppressing inflammatory infiltrates, specifically interleukin-17 (IL-17) secreting cells, and a myriad of inflammatory cytokines/mediators, and recruiting regulatory T cells (Tregs) at the colonic sites. In another disease model of mucosal inflammation induced by chemotherapy, we observed a significant reversal of AT mucositis and regain of body weight in nearly 100% of mice undergoing an exploratory one dose treatment with GMSC Experimental Approaches: We will examine the immunomodulatory effects of GMSC on Treg and Th17 functions and how they contribute to mucositis using both in vitro and in vivo studies. Optical coherence tomography (OCT) coupled with multiphoton microscopy (MMP) technology will be utilized to decipher stem cell homing to mucositic sites. We will test whether adaptive transfer with Pan-T cells, ex vivo expanded Tregs, and pharmacologic immune boosting therapies can reverse mucosal injuries.