胸腺类器官培养及应用进展

Culture and application of thymic organoids: a review

摘要:

胸腺是人体重要的免疫器官，是T细胞分化成熟的场所，受损后容易引发自身免疫性疾病甚至恶性肿瘤。多年来，研究人员主要通过T细胞体外单层培养系统探索T细胞的发育过程，揭示胸腺损伤和再生的机制。但单层培养系统既不能重现胸腺独特的三维上皮性网状结构，也无法充分提供造血干细胞定向分化为T细胞所需的细胞因子和生长因子。胸腺类器官技术利用具有干细胞潜能的细胞，在体外通过三维培养模拟胸腺的解剖结构和胸腺上皮细胞介导的信号通路，与体内胸腺微环境十分接近。在研究T细胞分化和发育、胸腺相关疾病、重建机体免疫功能以及细胞治疗等方面，胸腺类器官呈现出巨大潜力。文中系统介绍了胸腺类器官的培养方法，比较了培养所用支架的优缺点；同时探讨了胸腺类器官在疾病建模、肿瘤靶向治疗、再生医学和器官移植等领域的应用，并对其前景进行展望。

Abstract:

The thymus is a pivotal immune organ of the human body, and it is the place where T cells differentiate and mature. The damage of thymus would easily induce autoimmune diseases and even malignant tumors. For years, researchers have been exploring the process of T cell development and revealing the mechanism of thymic injury and regeneration generally through the monolayer culture system of T cells in vitro. However, the classic monolayer culture system could neither reproduce the unique three-dimensional epithelial reticular structure of the thymus, nor provide the cytokines and growth factors required for the directed differentiation of hematopoietic stem cells into T cells. Thymic organoid technology utilizes cells with stem cell potential to simulate the anatomical structure of the thymus and the signaling pathway mediated by thymic epithelial cells in vitro through three-dimensional culture, which is particularly close to the microenvironment of the thymus in vivo. Thymic organoids show great potential in the study of T cell differentiation and development, thymus-related diseases, reconstruction of immune function, and cell therapy. This paper summarizes the methods for culturing thymic organoids, followed by comparing the advantages and disadvantages of the scaffolds used for culturing. The applications of thymic organoids in the disease model, tumor-targeting therapy, regenerative medicine, and organ transplantation were also discussed, with possible future research directions prospected.