Thymic Epithelial Cells Induced from Pluripotent Stem Cells by a Three-Dimensional Spheroid Culture System Regenerates Functional T Cells in Nude Mice

Cellular Reprogramming
Motohito OkabeKen-Ichi Isobe

Abstract

The thymus is mainly composed of two types of epithelial cells, medullary thymic epithelial cells and cortex thymic epithelial cells (mTECs and cTECs). The tissue structure and mechanism for T cell development are complicated, with generation of the thymus regulated by complex molecular and cellular interactions of the thymic microenvironment during embryogenesis. Since the development of organ regeneration techniques became available, complete in vitro regeneration of the thymus has been attempted. Steric induction systems are thought to be optimal for tissue regeneration, but three-dimensional (3-D) induction of TECs from induced pluripotent stem cells (iPSCs) has not yet been reported. Here, we demonstrate the induction of functional TECs from iPSCs by a 3-D spheroid culture system with recruitment of robust numbers of T cells into the peripheral blood. Purified iPSC-derived TECs showed a sufficient expression level of FoxN1 comparable to TECs, and phenotypic analysis revealed that iPSC-derived TECs were expressing K5. Moreover, transplants of cell aggregations into recipient mice were not rejected and there was normal support of T cell development. Functional analysis revealed that T cells showed immune tolerance to both do...Continue Reading

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Citations

Aug 17, 2016·Current Stem Cell Reports·Asako TajimaYong Fan
Oct 6, 2012·Seminars in Cell & Developmental Biology·Yann BarrandonAriane Rochat
Jan 13, 2017·Orphanet Journal of Rare Diseases·Ioanna A Rota, Fatima Dhalla
Jul 27, 2021·Advanced Science·Himal Sharma, Lorenzo Moroni

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Methods Mentioned

BETA
genetic modification
flow cytometry

Software Mentioned

FlowJo

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