HMGB1介导TLR4/NF-κB通路在利用xTDM-aDFCSs复合体再生生物牙根中免疫调控相关研究

项目名称： HMGB1介导TLR4/NF-κB通路在利用xTDM-aDFCSs复合体再生生物牙根中免疫调控相关研究

项目编号： No.31470947

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 郭维华

作者单位： 四川大学

项目金额： 80万元

中文摘要： 免疫诱导耐受是组织器官再生关键。牙源性间充质干细胞具有抑制同种异体T、B、NK细胞特性，生物支架对宿主局部组织再生具有免疫调节作用，但细胞-生物支架复合物的免疫调控机制仍不清楚。HMGB1是典型的DAMPs,与受体RAGE、TLR2 和TLR4结合，激活核因子κB（NF-κB）,引发相应免疫反应，调控组织再生。本项目组前期研究利用同种异体牙囊细胞/膜片-牙本质基质复合物成功再生生物牙根，但利用同种异体牙囊细胞膜片-异种牙本质基质支架复合物是否能再生生物牙根仍不清楚，对其诱导的相关免疫调控机制尚需探究。本项目拟在前期研究基础上，以大鼠、小型猪及猕猴为动物模型，利用同种异体牙囊细胞膜片及异种牙本质基质支架再生生物牙根，重点研究此过程中HMGB1介导TLR4/ NF-κB通路的免疫调控机制。完善生物牙根再生策略，其意义在于为生物牙根临床前期实验奠定理论及生物技术基础，为临床应用提供理论技术指导。

中文关键词： 组织工程；支架材料；口腔再生医学

英文摘要： Immune induction and tolerance is the key for tissue or organ regeneration. Dental derived mesenchymal stem cells have immune regulation effect on proliferation of allogeneic cells such as T lymphocytes, B lymphocytes and NK cells. Similarly, biological scaffold could regulate local surrounding tissue immune response. However, the immunoregulation mechanism of combination of biological scaffold with cells is unclear. HMGB1, classical DAMPs(damage associated molecular patterns), combine with receptors RAGE, TLR2, TLR4 , thus activates nuclear transcription factor NF-κB to induce immune response and tissue remolding. Our previous studies have successfully regenerated biological tooth root by allogeneic dentin derived material (TDM) combined with allogeneic dental follicle cells or cell sheets, but it is unclear that whether xenogeneic TDM combined with allogeneic dental follicle cell sheets can regenerate tooth root, and its relevant mechanism is still need to explore. The present study will achieve tooth root regeneration by allogeneic dental follicle cells or cell sheets combined with xenogeneic TDM based on previous research, using rat, miniature pig, and monkey as animal model. This research focus on the immunoregulation mechanism of HMGB1 mediating TLR4/NF-κB signaling pathway, which provide theoretical and technical guidance for pre-clinical experiment of tooth root regeneration to complete strategy for clinical application of tooth root regeneration.

英文关键词： Tissue engineering;scaffold materials;Oral regenerative medicine