Derivation of Diverse Hormone-Releasing Pituitary Cells from Human Pluripotent Stem Cells.
Derivation of Diverse Hormone-Releasing Pituitary Cells from Human Pluripotent Stem Cells.
复制标题
从人类多能干细胞中衍生出多种释放激素的垂体细胞。
DOI：
10.1016/j.stemcr.2016.05.005
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发表时间：
2016-06-14
影响因子：
5.9
通讯作者：
Studer L
中科院分区：
文献类型：
--
作者：
Zimmer B;Piao J;Ramnarine K;Tomishima MJ;Tabar V;Studer L
人类多能干细胞（hPSC）为再生医学提供了无限的细胞来源。产生激素的细胞特别适合于细胞疗法，并且垂体功能减退症（垂体功能的缺陷）代表了有希望的治疗靶点。先前的研究已经使用3D类器官培养物从小鼠和人类ESC中衍生出垂体谱系，所述3D类器官培养物模拟体内垂体腺发育的复杂事件。而不是依赖于未知的细胞信号，我们提出了一个简单而有效的策略，从hPSC获得人垂体谱系使用单层培养条件适合细胞制造。我们证明，纯化基板细胞可以直接进入垂体的命运使用定义的信号。hPSC衍生的垂体细胞在体外显示基础和刺激诱导的激素释放，并且在移植到垂体功能减退的小鼠模型中后在体内显示植入和激素释放。这项工作奠定了基础，为未来的细胞治疗应用于垂体功能减退症患者。从hPSC中获得垂体前叶谱系细胞的已定义的cGMP就绪方案FGF 8和BMP 2图案化使得能够富集特异性垂体生成细胞垂体前叶细胞分泌多种激素并对生理刺激作出反应hPSC-垂体细胞部分地拯救垂体功能减退症的大鼠模型在这篇文章中，Studer及其同事提出了在cGMP-1作用下从hPSC衍生垂体前叶细胞。通过模拟体内发育模式线索，准备好单层条件。单细胞基因表达分析证实了体外产生的垂体细胞的身份和多样性。所产生的细胞在体外是功能性的，并且能够部分挽救垂体功能减退的大鼠模型。
Human pluripotent stem cells (hPSCs) provide an unlimited cell source for regenerative medicine. Hormone-producing cells are particularly suitable for cell therapy, and hypopituitarism, a defect in pituitary gland function, represents a promising therapeutic target. Previous studies have derived pituitary lineages from mouse and human ESCs using 3D organoid cultures that mimic the complex events underlying pituitary gland development in vivo. Instead of relying on unknown cellular signals, we present a simple and efficient strategy to derive human pituitary lineages from hPSCs using monolayer culture conditions suitable for cell manufacturing. We demonstrate that purified placode cells can be directed into pituitary fates using defined signals. hPSC-derived pituitary cells show basal and stimulus-induced hormone release in vitro and engraftment and hormone release in vivo after transplantation into a murine model of hypopituitarism. This work lays the foundation for future cell therapy applications in patients with hypopituitarism. Defined, cGMP-ready protocol to derive anterior pituitary-lineage cells from hPSCs FGF8 and BMP2 patterning enables enrichment for specific hormone-producing cells Pituitary cells secrete multiple hormones and respond to physiological stimuli hPSC-pituitary cells partially rescue a rat model of hypopituitarism In this article, Studer and colleagues present the derivation of anterior pituitary cells from hPSCs under cGMP-ready monolayer conditions by mimicking in vivo developmental patterning cues. Single-cell gene-expression analysis confirms identity and diversity of in vitro generated pituitary cells. The generated cells are functional in vitro and capable of partially rescuing a rat model of hypopituitarism.