Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells.
Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells.
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DOI：
10.1038/ncomms10351
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发表时间：
2016-01-14
影响因子：
16.6
通讯作者：
Sasai Y
中科院分区：
文献类型：
--
作者：
Ozone C;Suga H;Eiraku M;Kadoshima T;Yonemura S;Takata N;Oiso Y;Tsuji T;Sasai Y
垂体前叶对内分泌系统至关重要。它的激素反应的积极和消极的监管机构是必不可少的稳态。由于这个原因，在体外产生保留调节激素控制的人垂体前叶组织是发展垂体疾病的细胞移植疗法的重要一步。在这里，我们通过使用人类胚胎干细胞重现小鼠垂体发育来实现这一点。我们发现，垂体前叶自我形式在体外共同诱导下丘脑和口腔外胚层。这些组织的并列促进垂体基板的形成，随后分化成垂体腺瘤产生细胞。它们对释放信号和反馈信号的反应都很正常。此外，在移植到低血糖小鼠后，体外产生的促肾上腺皮质激素细胞挽救了宿主的身体活动水平和存活率。因此，我们报告了一个有用的方法，生产调节器响应人类垂体组织，可能有利于未来的研究再生医学。 体外培养人垂体前叶组织是一个困难的过程。在这里，Ozone等人通过重现体内发育从胚胎干细胞中产生人类垂体前叶，并证明这种组织分泌激素，并在移植到小鼠体内时挽救垂体功能减退症。
Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine. It is difficult to generate functional human anterior pituitary tissues in vitro. Here, Ozone et al. generate human anterior pituitary from embryonic stem cells by recapitulating in vivo development, and demonstrate this tissue secretes hormones and rescues hypopituitarism when grafted into mice.