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

Nicholas Bredenkamp, Xin Jin, Dong Liu, Kathy E O'Neill, Nancy R Manley, Catherine Clare Blackburn

Research output: Contribution to journalLiterature reviewpeer-review

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.

Original languageEnglish
Pages (from-to)317-29
Number of pages13
JournalRegenerative medicine
Volume10
Issue number3
DOIs
Publication statusPublished - 1 May 2015

Keywords

  • directed differentiation
  • direct reprogramming
  • microenvironment
  • pluripotent stem cell
  • progenitor cell
  • stem cell
  • thymic epithelial cell
  • thymus

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