REVERSAL OF MUCOSITIS BY GMSC-BASED THERAPY

基于 GMSC 的疗法逆转粘膜炎

• 批准号: 8362697
• 负责人: PETRA E WILDER-SMITH
• 金额: $ 0.31万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362697
• 关键词: Adverse effects; Biotechnology; Body Weight; Bone Marrow Transplantation; California; Cell Therapy; Cells; Clinical; Colitis; Coupled; Disease model; Dose; Exhibits; Funding; Gastrointestinal tract structure; Gingiva; Grant; Head and neck structure; Homing; Immune; In Vitro; Inflammation; Inflammatory; Inflammatory Infiltrate; Injury; Interleukin-17; Laboratories; Lasers; Mediator of activation protein; Microscopy; Molecular Biology; Mucositis; Mus; National Center for Research Resources; Optical Coherence Tomography; Patients; Principal Investigator; Radiation; Recruitment Activity; Regulatory T-Lymphocyte; Research; Research Infrastructure; Resources; School Dentistry; Severities; Site; Source; Stem cells; T-Lymphocyte; Technology; Testing; Tissues; United States National Institutes of Health; Universities; base; cancer therapy; chemotherapy; cost; craniofacial; cytokine; human stem cells; in vivo; self-renewal; stem cell population

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 南加州大学牙科学院颅面分子生物学中心 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能力，但也具有独特的免疫调节功能。基于细胞的GMSC的细胞治疗可显着改善实验性鼠结肠炎中结肠炎症的临床和组织病理严重程度，可能是通过抑制炎性浸润性的，特异性介绍性炎性细胞（IL-17）的分泌细胞，以及无数的炎症细胞因子/媒体/媒体/介导者/定位的细胞。在化学疗法引起的另一个粘膜炎症的疾病模型中，我们观察到粘膜炎的显着逆转和体重恢复，近100％的小鼠接受了一种探索性一剂量治疗的GMSC 实验方法：我们将检查GMSC对TREG和TH17功能的免疫调节作用，以及它们如何使用体外和体内研究对粘膜炎有效。光学相干断层扫描（OCT）以及多光子显微镜（MMP）技术将用于将干细胞归巢于粘膜位点。我们将测试使用PAN-T细胞的自适应转移，体内扩展的Tregs以及药理学的免疫促进疗法是否会逆转粘膜损伤。