基于牙周微环境调节的牙周组织再生研究

项目名称： 基于牙周微环境调节的牙周组织再生研究

项目编号： No.81470751

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘怡

作者单位： 首都医科大学

项目金额： 100万元

中文摘要： 基于干细胞的牙周组织再生是口腔科学的研究重点之一，目前调控因素不清，再生效果不稳定，限制其应用前景。宿主免疫系统新近被证明是制约组织工程修复的重要因素之一，而牙周微环境由于受到牙周微生物的影响更加复杂。本转化医学课题基于前期关于宿主免疫在组织工程中发挥重要作用的研究基础，进一步探讨牙周微生态、干细胞及宿主免疫之间的相关关系，并通过牙周微生态调节和宿主免疫干预促进基于干细胞的再生效果。本课题拟利用小鼠及大鼠为实验动物模型，通过体外共培养系统研究牙周微生态系对牙周干细胞及宿主免疫的影响，发现关键调控机制，并在大鼠牙周再生模型上进行验证，进一步探讨通过调节牙周微生态系及宿主免疫，促进基于牙周干细胞的牙周组织缺损再生的方法。本申请研究有望发现在干细胞介导牙周骨缺损修复中，牙周微生态及宿主免疫调节的关键机制及有效干预手段，为组织工程技术成功应用于牙周再生提供新策略及科学依据。

中文关键词： 牙周病；牙周再生；间充质干细胞；牙周组织工程

英文摘要： Regeneration and reconstruction of periodontal tissues are most important and difficult issues in clinic therapy. Periodontal ligament stem cell (PDLSC)-based tissue engineering is the one of directions of periodontal therapy. Until now, the instability of therapeutic effects limited the application of tissue engineering, and the critical negative factors are unclear. Based on our previous studies, we propose to investigate the critical role of periodontal microenvironment on the periodontal tissue reparation and reconstruction in PDLSC-based tissue engineering, and try to find the new clinic therapeutic to improve the effects of cell-based periodontal tissue engineering via host periodontal microenvironment. Several periodontal bacteria (including periodontal pathogenic bacteria and beneficial bacteria) were selected and cocultured with mouse gingiva mesenchymal stem cells (GMSCs) and actived T cells in vitro. The influences of different periodontal bacteria on GMSCs and T cells were observed, and the critical factors to control the capability of periodontal tissue healing and bone regeneration would be dissected, and mechanism would be investigated in detail. The mouse periodontitis models would be used to confirm the critical factors and the mechanism. In order to confirm the mechanism which had been found from mouse periodontitis model, a stable periodontitis bone defect models would be established on the rat maxillary first molars, and PDLSCs would be harvested and cultured from rat periodontal ligament tissues. To repair and reconstruct periodontal tissues, autogenic or allogenic PDLSCs combined with gelfoam were hired to fill into the position of alveolar bone defect. The therapeutic methods to modulate the microenvironment (including bacteria components and host immune system) would be applied on these rat models. The reparation and regeneration effects of periodontal tissues would be evaluate via histological and immunohistological methods, X-ray and MicroCT images. The results may provide the important insight for the clinic therapy of periodontal diseases and cell-based periodontal tissue engineering, and the critical role of periodontal microenvironment during tissue engineering will be highlighted in the flied of periodontal tissues regeneration.

英文关键词： periodontitis;periodontal tissue regeneration;mesenchymal stem cell;periodontal tissue engineering