Testicular organoid generation by a novel in vitro three-layer gradient system
Testicular organoid generation by a novel in vitro three-layer gradient system
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DOI：
10.1016/j.biomaterials.2017.03.025
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发表时间：
2017-06-01
期刊：
影响因子：
14
通讯作者：
Stukenborg, Jan-Bernd
中科院分区：
文献类型：
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作者：
Alves-Lopes, Joao Pedro;Soder, Olle;Stukenborg, Jan-Bernd
睾丸微环境和精原干细胞（SSC）的生态位在体外模型的系统尚未产生。在这里，我们开发并表征了一种新型的三维多层模型，三层梯度系统（3-LGS），它允许生成具有功能性血睾屏障（BTB）和生殖细胞建立和增殖的大鼠睾丸类器官。该模型是独特的，关于细胞组织的形成，更密切地代表在体外的体内生殖细胞到体细胞协会。此外，我们还验证了维甲酸（RA），IL-1 α，TNF α和RA抑制剂在生殖细胞的维护和BTB组织在体外的作用。RA治疗有利于生殖细胞的维持，而IL-1 α和TNF α则会损害睾丸类器官的形成和生殖细胞的维持。考虑到我们的表征和验证结果，我们提出了3-LGS作为一个新的平台，在体外研究SSC生态位，并寻找新的未知因素参与生殖细胞增殖和分化。此外，我们建议该模型可用于其他科学领域，通过类器官的产生来研究器官发生和发育。(C)2017作者（S）由爱思唯尔有限公司发布
A system that models the testicular microenvironment and spermatogonial stem-cell (SSC) niche in vitro has not been produced yet. Here, we developed and characterized a novel three-dimensional multilayer model, the Three-Layer Gradient System (3-LGS), which permits the generation of rat testicular organoids with a functional blood-testis barrier (BTB) and germ cell establishment and proliferation. The model is unique as regards the formation of cellular organizations that more closely represent the in vivo germ-to-somatic cell associations in vitro. Moreover, we also verified the roles of retinoic acid (RA), IL-1 alpha, TNF alpha and RA inhibitors in germ cell maintenance and BTB organization in vitro. Treatment with RA was beneficial for germ cell maintenance, while IL-1 alpha and TNF alpha were observed to impair the formation of testicular organoids and germ cell maintenance. Taking in account our characterization and validation results, we propose the 3-LGS as a new platform to investigate the SSC niche in vitro and to search for novel unknown factors involved in germ cell proliferation and differentiation. Moreover, we suggest that this model can be used in other scientific fields to study organogenesis and development by the generation of organoids. (C) 2017 The Author(s). Published by Elsevier Ltd.