Construction of a functional thymic microenvironment from pluripotent stem cells for the induction of central tolerance.
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.
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.
Nicholas
N
Bredenkamp
Xin
X
Jin
Dong
D
Liu
Kathy E
KE
O'Neill
Nancy R
NR
Manley
Catherine Clare
CC
Blackburn
D000818:Animals; D065150:Cellular Reprogramming / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D009940:Organoids / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000276:immunology; D055153:Stem Cell Niche / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000637:transplantation
direct reprogramming; directed differentiation; microenvironment; pluripotent stem cell; progenitor cell; stem cell; thymic epithelial cell; thymus