基于iPS细胞体外构建工程化淋巴组织的实验研究

项目名称： 基于iPS细胞体外构建工程化淋巴组织的实验研究

项目编号： No.31200733

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 郝彤

作者单位： 中国人民解放军军事医学科学院

项目金额： 23万元

中文摘要： 近年来，淋巴组织体外三维再造研究进展迅速。再造淋巴组织在免疫系统相关疾病治疗、疫苗与佐剂体外评价模型等方面具有重要应用前景。已有研究报道表明，iPS细胞在体外可分化为淋巴细胞，而Notch信号通路活化则在淋巴细胞发育过程中发挥重要作用。本项目拟首先开展iPS向淋巴细胞诱导分化的研究，再以iPS诱导分化来源的淋巴细胞作为种子细胞、胶原凝胶和/或壳聚糖大孔材料为支架，体外构建工程化淋巴组织，并通过组织学、免疫组织化学及分子生物学方法，对再造工程化淋巴组织进行结构与功能检测。在上述研究基础上，进一步探索iPS向淋巴细胞诱导分化过程中Notch信号通路活化的规律及其分子机制，并比较二维和三维培养环境对Notch信号通路活化的影响。本研究有望为利用iPS体外构建淋巴组织奠定基础，在未来临床免疫缺陷性疾病治疗及相应体外评价模型方面具有潜在应用前景。

中文关键词： 干细胞；支架材料；三维再造；淋巴细胞；分化

英文摘要： Recently, rapid progress has been made in the filed of lymphoid tissue reconstruction in vitro. Reconstructed lymphoid tissue has important application prospect in the immune system related diseases, vaccines and adjuvants evaluation of model in vitro. It has been reported that iPS cells can differentiate to lymphocytes in vitro, and the Notch signaling pathway plays an important role in the development of lymphocyte. The project will use iPS derived lymphocytes as seeding cells, collagen gel and/or chitosan as cell scarffold, to reconstruct lymphoid tissue in vitro, and evaluate its structure and function by histology, immunohistochemistry and molecular biology methods. Meanwhile, further study effect of the Notch signaling pathway on the process of iPS differenting to lymphocyte and its molecular mechanisms, and compare effect of two-dimensional and three-dimensional culture environment on the Notch signaling activation. This study is expected to lay the foundation for reconstructed lymphoid tissue by iPS and have potential application in the treatment of immunodeficiency disease and evaluation in vitro.

英文关键词： stem cells；scaffolds；three-dimensional reconstruction；lymphocytes；cell differentiation