Journal
CELL STEM CELL
Volume 13, Issue 2, Pages 219-229Publisher
CELL PRESS
DOI: 10.1016/j.stem.2013.04.004
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Funding
- Canadian Institutes of Health Research fellowship
- Richard G. Klein fellowship
- JDRF fellowship [3-2012-266]
- CIRM grant [CIRM RM1-01702]
- UCSF Diabetes and Endocrinology Research Center (DERC)
- UCSF Flow Cytometry Core
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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 TGF beta, 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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