Piccinini Elia, Bonfanti Paola
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, CA, USA.
Great Ormond Street Institute of Child Health, University College London, London, UK.
Methods Mol Biol. 2019;1899:129-142. doi: 10.1007/978-1-4939-8938-6_10.
This review briefly describes the last decades of experimental work on the thymus. Given the histological complexity of this organ, the multiple embryological origins of its cellular components and its role in carefully regulating T lymphocyte maturation and function, methods to dissect and understand this complexity have been developed through the years. The possibility to study ex vivo the thymus organ function has been achieved by developing Fetal Thymus Organ Cultures (FTOC). Subsequently, the combination of organ disaggregation and reaggregation in vitro represented by Reaggregate Thymus Organ cultures (RTOC) allowed mixing cellular components from different genetic backgrounds. Moreover, RTOC allowed dissecting the different stromal and hematological components to study the interactions between Major Histocompatibility Complex (MHC) molecules and the T-cell receptors during thymocytes selection. In more recent years, prospective isolation of stromal cells and thymocytes at different stages of development made it possible to explore and elucidate the molecular and cellular players in both the developing and adult thymus. Finally, the appearance of novel cell sources such as embryonic stem (ES) cells and more recently induced pluripotent stem (iPS) cells has opened new scenarios in modelling thymus development and regeneration strategies. Most of the work described was carried out in rodents and the current challenge is to develop equivalent or even more informative assays and tools in entirely human model systems.
本综述简要描述了过去几十年间关于胸腺的实验工作。鉴于该器官的组织学复杂性、其细胞成分的多种胚胎学起源以及它在精细调节T淋巴细胞成熟和功能方面的作用，多年来人们已开发出剖析和理解这种复杂性的方法。通过发展胎儿胸腺器官培养（FTOC）实现了在体外研究胸腺器官功能的可能性。随后，以重组胸腺器官培养（RTOC）为代表的体外器官解离和重组相结合的方法，使得来自不同遗传背景的细胞成分得以混合。此外，RTOC能够剖析不同的基质和血液学成分，以研究胸腺细胞选择过程中主要组织相容性复合体（MHC）分子与T细胞受体之间的相互作用。近年来，对处于不同发育阶段的基质细胞和胸腺细胞进行前瞻性分离，使得探索和阐明发育中的胸腺及成年胸腺中的分子和细胞参与者成为可能。最后，诸如胚胎干细胞（ES细胞）以及最近的诱导多能干细胞（iPS细胞）等新型细胞来源的出现，为胸腺发育建模和再生策略开辟了新的前景。所述的大部分工作是在啮齿动物中进行的，当前的挑战是在完全的人类模型系统中开发等效甚至更具信息性的检测方法和工具。
