OSTEOGENIC AND IMMUNOMODULATORY PROPERTIES OF DECIDUOUS TOOTH STEM CELLS

描述(申请人提供)：颅面骨缺损的修复需求很大.尽管最近的研究表明间充质干细胞(MSC)可用于修复动物模型中的颅骨缺损，但通常用于修复口腔颌面部骨缺损的轴骨和附件骨自体移植往往效果不佳。从口腔面部供体部位获取的移植物桥接口腔面部缺损通常比从非口腔面部供体部位获得的移植物更成功，这表明解剖骨骼部位的不同影响了移植物的整合。人脱皮乳牙干细胞具有MSC特性，并表现出极高的增殖能力，提示少量培养扩增可为临床提供足够数量的细胞。因此，SHEAT有望成为修复面神经冠相关骨缺损的一种合适的干细胞来源。我们的初步数据表明，Share的再生和免疫调节特性受端粒酶活性的调节。因此，我们的假设是，通过了解端粒酶调节Share成骨分化和免疫调节的机制，可以显著促进基于Share的组织再生。在这项应用中，我们将描述激活端粒酶活性促进脱落介导骨再生修复颅骨缺损的机制。根据我们的新发现，端粒酶调控Share的免疫调节功能，我们将研究端粒酶如何调控Share介导的免疫调节。最后，我们将把受体免疫调节与基于棚子的组织再生联系起来。总而言之，我们建议的研究中的新发现将为理解基于棚的疗法提供分子基础。意义：这些研究最有可能导致：1)揭示端粒酶相关途径调控SHEAD成骨和免疫调节的新分子机制；2)开发新的治疗策略，以突破通过调节受体T细胞促进颅骨再生的关键障碍。

DESCRIPTION (provided by applicant): There is a great demand thefor the repair of craniofacial bone defects. Despite the recent studies suggest that mesenchymal stem deciduous teeth (MSC) could be used to repair cranial defects in animal models, autologous grafts from axial and appendicular bones commonly used to repair orofacial bone defects often result in an unfavorable outcome. Bridging orofacial defects with grafts obtained from an orofacial donor site are usually more successful than those from non-orofacial sites, indicating that anatomic skeletal site-specific differences affect graft integration. Stem cells from Human Exfoliated Deciduous teeth (SHED) possess MSC characteristics and show extremely high proliferation capacity, suggesting that culture expanded small number of SHED can provide sufficient number of cells for clinical use. Therefore, SHED would be an appropriate accessible stem cell resource for repairing neural crest-related orofacial bone defects. Our preliminary data showed that regenerative and immunomodulatory properties of SHED are regulated by telomerase activity. Therefore, our hypothesis is that SHED-based tissue regeneration can be significantly improved with understanding mechanism by which telomerase regulates osteogenic differentiation and immunomodulation of SHED. In this application, we will characterize the mechanism by which activation of telomerase activity improves SHED-mediated bone regeneration for repairing calvarial defects. On the basis of our novel findings that telomerase governs immunomodulatory function of SHED, we will examine how telomerase controls SHED-mediated immune regulation. Finally, we will link recipient immunoregulation to SHED-based tissue regeneration. Collectively, novel findings from our proposed studies will provide a molecular basis for understanding SHED-based therapies. Significance: These studies will most likely lead to: 1) unveiling novel molecular mechanisms by which telomerase associated pathways govern osteogenesis and immunomodulation of SHED; and 2) developing new therapeutic strategies to break through the critical barrier for improving calvarial bone regeneration via regulation of recipient T cells.