Primary Human Testicular Cells Self-Organize into Organoids with Testicular Properties.

Primary Human Testicular Cells Self-Organize into Organoids with Testicular Properties.
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DOI:
10.1016/j.stemcr.2016.11.012
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发表时间:
2017-01-10
期刊:
影响因子:
5.9
通讯作者:
Goossens E
Goossens E
中科院分区:
医学1区
文献类型:
--
作者:
Baert Y;De Kock J;Alves-Lopes JP;Söder O;Stukenborg JB;Goossens E

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到目前为止,只有在啮齿动物中成功地从头形成睾丸组织,然后在体外完成精子发生。我们的研究结果表明,原代人类睾丸细胞能够自组织成人类睾丸类器官(TO),即,多细胞组织替代物,有或没有生物支架的支持。尽管缺乏睾丸特定的地形,这些微型组织窝藏精原细胞和它们的重要的生态位细胞,保留在长期培养的特定功能。这些观察结果表明,在体外重建的人睾丸微环境的原代细胞的可能性。人类TO可能有助于仿生睾丸模型的开发,这将对研究和开发、不孕症的临床治疗以及与药物发现和毒理学相关的筛选产生巨大影响。原代人睾丸细胞形成类器官,而不管支架的支持。睾丸特异性的细胞结构在睾丸类器官中没有恢复。活性的小生境细胞和精原细胞在睾丸类器官中得以维持。睾丸类器官可能有助于实现体外人类精子发生。Baert和他的同事表明,原代人类睾丸细胞自组装成半-具有睾丸活动的有组织的类器官,有或没有生物支架的支持。睾丸类器官可能有助于开发一种睾丸模型,可用于研究精子发生或其疾病,作为男性不育症的治疗方法,以及用于药物发现和毒理学的筛选。
So far, successful de novo formation of testicular tissue followed by complete spermatogenesis in vitro has been achieved only in rodents. Our findings reveal that primary human testicular cells are able to self-organize into human testicular organoids (TOs), i.e., multi-cellular tissue surrogates, either with or without support of a biological scaffold. Despite lacking testis-specific topography, these mini-tissues harbored spermatogonia and their important niche cells, which retained specific functionalities during long-term culture. These observations indicate the posibility of in vitro re-engineering of a human testicular microenvironment from primary cells. Human TOs might help in the development of a biomimetic testicular model that would exert a tremendous impact on research and development, clinical treatment of infertility, and screening in connection with drug discovery and toxicology. Primary human testicular cells form organoids regardless of scaffold support The testis-specific cytoarchitecture was not restored in testicular organoids Active niche cells and spermatogonia were maintained in testicular organoids Testicular organoids might help achieving human spermatogenesis in vitro In this article, Baert and colleagues show that primary human testicular cells self-assemble to semi-organized organoids with testicular activities with or without support from a biological scaffold. Testicular organoids might help developing a testicular model which can be used to study spermatogenesis or its disorders, as a treatment for male infertility, and for screening in drug discovery and toxicology.