Physioxia enhances T-cell development ex vivo from human hematopoietic stem and progenitor cells

Dong Yeop Shin, Xinxin Huang, Chang Hyun Gil, Arafat Aljoufi, James Ropa, Hal E. Broxmeyer

Research output: Contribution to journalArticle

Abstract

Understanding physiologic T-cell development from hematopoietic stem (HSCs) and progenitor cells (HPCs) is essential for development of improved hematopoietic cell transplantation (HCT) and emerging T-cell therapies. Factors in the thymic niche, including Notch 1 receptor ligand, guide HSCs and HPCs through T-cell development in vitro. We report that physiologically relevant oxygen concentration (5% O2, physioxia), an important environmental thymic factor, promotes differentiation of cord blood CD34+ cells into progenitor T (proT) cells in serum-free and feeder-free culture system. This effect is enhanced by a potent reducing and antioxidant agent, ascorbic acid. Human CD34+ cell-derived proT cells in suspension cultures maturate into CD3+ T cells in an artificial thymic organoid (ATO) culture system more efficiently when maintained under physioxia, compared to ambient air. Low oxygen tension acts as a positive regulator of HSC commitment and HPC differentiation toward proT cells in the feeder-free culture system and for further maturation into T cells in the ATO. Culturing HSCs/HPCs in physioxia is an enhanced method of effective progenitor T and mature T-cell production ex vivo and may be of future use for HCT and T-cell immunotherapies.

Original languageEnglish (US)
JournalSTEM CELLS
DOIs
StateAccepted/In press - 2020

Keywords

  • cord blood
  • differentiation
  • hematopoietic stem and progenitor cells
  • hypoxia
  • physioxia
  • progenitor T cells
  • T cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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