成牙诱导潜能的分子构成及再生牙的制备

人类牙齿的再生是一项极具应用前景、市场价值和社会效益的研究。人牙源性间充质干细胞不具备诱导牙齿发育潜能，只具备被诱导分化形成相关牙组织的能力，无法利用这些干细胞，像牙胚细胞的再生体系那样，重建完整的牙齿器官。因此，解析成牙诱导潜能的分子构成已经成为牙齿再生研究中亟待解决的科学问题。本项目将在前期研究的基础上，解析成牙诱导潜能的分子构成，通过RNAi修饰、过表达相关转录因子和添加生长因子蛋白等，赋予牙髓干细胞诱导牙齿发育潜能，使牙髓干细胞获得牙胚细胞的特性，与iPSCs混合重组，构建组织工程牙胚，植入裸鼠肾囊膜下培育，尝试异位重建完整的牙齿器官，并进行再生牙的生物学特性评估。研究结果将为理解牙齿再生的机理提供实验数据，为进一步的临床研究奠定理论和技术基础，对干细胞在组织工程领域中的应用研究也有普遍的意义。

Stem cell based tooth regeneration will have great clinical application in regenerative dental medicine in the near future. There are five types of tooth-derived mesenchymal stem cells that have been isolated and characterized so far. While these stem cells can be induced to differentiate into mesenchyme-derived tooth tissues, none of them possess tooth inductive capability, the odontogenic potential,to induce tissues of non-dental origin to form a tooth.Therefore, identification of the molecular components of odontogenic potential will be the prerequisite for future realization of stem cell based tooth regeneration in humans. In this application, built on our previous and preliminary studies, we will identify and characterize factors that constitute the odontogenic potential, and further confer dental pulp stem cells with odontogenic potential. Dental pulp stem cells that acquire odontogenic potential will be recombined with iPSCs to construct tooth germs and subject to kidney capsule culture in nude mice to generate tooth organs. Our ultimate goal is to develop cell-based strategies to replace missing teeth in humans. These studies will have great impact on the practice of human tooth regeneration in the near future, and will also have general implication in stem cell based tissue engineering.