Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development.
Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development.
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DOI：
10.1016/j.stem.2013.04.004
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发表时间：
2013-08-01
期刊：
影响因子：
23.9
通讯作者：
Hebrok, Matthias
中科院分区：
文献类型：
--
作者：
Parent, Audrey V.;Russ, Holger A.;Khan, Imran S.;LaFlam, Taylor N.;Metzger, Todd C.;Anderson, Mark S.;Hebrok, Matthias
诱导免疫耐受以防止排斥反应是在临床环境中成功移植干细胞来源组织的关键步骤。利用人类多能干细胞产生能够支持T细胞发育的胸腺上皮细胞（TECs）是实现这一目标的一种有希望的方法；然而，在生成功能性tec方面的进展有限。在这里，我们描述了一种强大的体外方法，通过精确调节TGFβ、BMP4、RA、Wnt、Shh和FGF信号传导，直接将人胚胎干细胞（hESCs）分化为胸腺上皮祖细胞（TEPs）。hesc衍生的TEPs在移植到胸腺缺陷小鼠后进一步成熟为支持T细胞发育的功能性tec。重要的是，移植的TEPs产生了能够在体外增殖以及体内免疫反应的T细胞。因此，hesc衍生的TEP移植物可能具有广泛的应用，可以增强细胞疗法的植入，以及恢复年龄和压力相关的胸腺衰退。
Inducing immune tolerance to prevent rejection is a key step toward successful engraftment of stem-cell-derived tissue in a clinical setting. Using human pluripotent stem cells to generate thymic epithelial cells (TECs) capable of supporting T cell development represents a promising approach to reach this goal; however, progress toward generating functional TECs has been limited. Here, we describe a robust in vitro method to direct differentiation of human embryonic stem cells (hESCs) into thymic epithelial progenitors (TEPs) by precise regulation of TGFβ, BMP4, RA, Wnt, Shh, and FGF signaling. The hESC-derived TEPs further mature into functional TECs that support T cell development upon transplantation into thymus-deficient mice. Importantly, the engrafted TEPs produce T cells capable of in vitro proliferation as well as in vivo immune responses. Thus, hESC-derived TEP grafts may have broad applications for enhancing engraftment in cell-based therapies as well as restoring age-and stress-related thymic decline.
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影响因子：
23.9
作者：
Longmire, Tyler A.;Ikonomou, Laertis;Hawkins, Finn;Christodoulou, Constantina;Cao, Yuxia;Jean, J. C.;Kwok, Letty W.;Mou, Hongmei;Rajagopal, Jayaraj;Shen, Steven S.;Dowton, Anne A.;Serra, Maria;Weiss, Daniel J.;Green, Michael D.;Snoeck, Hans-Willem;Ramirez, Maria I.;Kotton, Darrell N.
通讯作者：
Kotton, Darrell N.
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影响因子：
23.9
作者：
Mou, Hongmei;Zhao, Rui;Sherwood, Richard;Ahfeldt, Tim;Lapey, Allen;Wain, John;Sicilian, Leonard;Izvolsky, Konstantin;Musunuru, Kiran;Cowan, Chad;Rajagopal, Jayaraj
通讯作者：
Rajagopal, Jayaraj
影响因子：
64.5
作者：
Calderon, Lesly;Boehm, Thomas
通讯作者：
Boehm, Thomas
影响因子：
56.9
作者：
Nehls, M;Kyewski, B;Boehm, T
通讯作者：
Boehm, T
DOI：
10.1073/pnas.0605159103
发表时间：
2006-12-12
影响因子：
11.1
作者：
Nobori, Shuji;Shimizu, Akira;Yamada, Kazuhiko
通讯作者：
Yamada, Kazuhiko