人牙龈成纤维细胞源的诱导多能干细胞实现牙周组织再生的研究

项目名称： 人牙龈成纤维细胞源的诱导多能干细胞实现牙周组织再生的研究

项目编号： No.81470739

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： 栾庆先

作者单位： 北京大学

项目金额： 73万元

中文摘要： 牙周病不但引起牙周支持组织的破坏，且可对全身健康造成威胁。传统的牙周治疗无法再生破坏的牙周组织。真正意义上的牙周组织再生要求形成新的牙骨质和牙槽骨，并且有新生的牙周膜纤维嵌入并连接新生的牙骨质及骨组织。以干细胞为基础、应用组织工程学原理是实现上述目标潜在、可行的手段，开展相关研究具有重要的现实意义。牙周组织细胞被认为是诱导多能干细胞(iPSCs)的理想细胞来源,并且其诱导的iPSCs具有重新分化为牙周支持组织的优势。本研究采用非整合性的转染方法建立人牙龈成纤维细胞来源的iPSCs，并通过体外研究探讨iPSCs在釉基质蛋白及重组人生长分化因子-5的作用下，向牙周组织定向分化的可能性，进而建立免疫缺陷大鼠牙周缺损模型，植入iPSCs、Bio-oss支架材料及生长因子，评价牙周组织细胞来源的iPSCs在动物体内实现牙周组织再生的效果，为进一步开展iPSCs在牙周再生治疗中的应用及临床转化提供理论基础。

中文关键词： 牙周组织再生；人牙龈成纤维细胞；诱导多能干细胞；支架材料；生长因子

英文摘要： Periodontal disease is dental plaque-induced infection and inflammation of tooth supporting tissues. Without timely treatment, periodontal disease can not only cause irreversible destruction of alveolar bone, periodontal ligament and gingiva, but also endanger the general health system. The true periodontal regeneration requires restoration of alveolar bone, periodontal ligament and cementum simultaneously with appropriate integration between the newly formed tissues,while traditional therapies are unable to regenerate damaged periodontal tissues and restore normal structure. Induced pluripotent stem cells (iPSCs) are considered to be an ideal source for periodontal regeneration, and may have the inclination of being differentiated into periodontal tissues. In our study, induced pluripotent stem cells (iPSCs) are generated by non-integrated transfection from human gingival fibroblasts.We plan to explore the possibility of directing the differentiation of iPSCs into specific periodontal cell lineages in vitro by application of enamel matrix derivatives (EMD) and recombinant human growth/differentiation factor-5 (rhGDF-5). Afterwards, iPSCs are seeded and cultured on Bio-oss scaffolds, and scaffold-cell constructs together with EMD or rhGDF-5 will be implanted into a periodontal fenestration defect in immunodeficient rat models to evaluate the regeneration of new periodontal tissues. The study will provide theoretical foundation for translational medicine and help to expand the clinical application of iPSCs in periodontal regeneration.

英文关键词： Periodontal Regeneration;Human Gingival Fibroblasts;Induced Pluripotent Stem Cells;Bio-oss Scaffold;Growth Factors