Construction of a functional thymic microenvironment from pluripotent stem cells for the induction of central tolerance.

Regen Med

MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh, EH16 4UU, UK.

Published: January 2016

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Article Abstract

The thymus is required for generation of a self-tolerant, self-restricted T-cell repertoire. The capacity to manipulate or replace thymus function therapeutically would be beneficial in a variety of clinical settings, including for improving recovery following bone marrow transplantation, restoring immune system function in the elderly and promoting tolerance to transplanted organs or cells. An attractive strategy would be transplantation of thymus organoids generated from cells produced in vitro, for instance from pluripotent stem cells. Here, we review recent progress toward this goal, focusing on advances in directing differentiation of pluripotent stem cells to thymic epithelial cells, a key cell type of the thymic stroma, and related direct reprogramming strategies.

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http://dx.doi.org/10.2217/rme.15.8DOI Listing

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