人毛囊真皮乳头细胞的体外分化与毛囊重建

项目名称： 人毛囊真皮乳头细胞的体外分化与毛囊重建

项目编号： No.31471287

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： 段恩奎

作者单位： 中国科学院动物研究所

项目金额： 85万元

中文摘要： 毛囊真皮乳头(dermal papilla,DP)是毛囊中一群特化的真皮成纤维细胞，在毛囊形态发生、性质决定及毛发周期调控中发挥重要作用，也与毛发疾病密切相关。目前脱发已成为日益普遍的社会现象，基于干细胞移植的毛囊重建是治疗脱发的一个极具潜力的方向。毛囊重建不仅需要毛囊表皮细胞，还需要能诱导毛囊形成的DP细胞，但DP细胞无法在体外大量扩增并保持其诱导能力。目前大多数研究致力于在体外扩增DP细胞并保持其特性，但效果远达不到临床需求。与这些研究不同，本项目将另辟蹊径，从可大量扩增的人多能性干细胞（ES细胞和iPS细胞）与人真皮成纤维细胞出发，在体外探究DP细胞的分化及转分化的过程与机制，并获得大量的DP细胞，结合我们已建立的毛囊干细胞体外扩增体系，进行异体毛囊重建实验。本项目将为揭示皮肤发育与更新过程中的上皮-间充质相互作用机制提供重要线索，在组织工程毛囊重建与脱发治疗领域更具有直接应用价值。

中文关键词： 毛囊真皮乳头；毛囊重建；干细胞分化；转分化；重编程

英文摘要： Hair follicle dermal papilla (DP) cells are specialized dermal fibroblasts, which play key roles in the morphogenesis and cyclic regulation of hair follicles and are closedly related to various hair diseases. Hair loss is an increasingly common human disease. Although stem cell-based hair follicle reconstitution provides a promising treatment for hair loss, the indispensable hair-inducing DP cells are hard to maintain and expand in vitro, which largely hampered their clinical use. Most of current studies aim at propagating DP cells in vitro while restoring their properties. In contrast, the present project intends to derive hair-inducing DP-like cells from human pluripotent stem cells and dermal fibroblasts, which could be easily expanded in vitro.Together with our established in-vitro system for hair follicle stem cell propagation, the present study pursues hair follicle reconstitution with in-vitro derived hair follicle epithelial cells and dermal mesenchymal cells. We shall meanwhile explore the mechanisms governing DP differentiation and trans-differentiation. Our project will not only help reveal the epithelial-mesenchymal interactions during skin development and homeostatsis, but also contribute greatly to the regenerative medical treatment for hair loss.

英文关键词： hair follicle dermal papilla;hair reconstitution;stem cell differentiation;trans-differentiation;reprogramming