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

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

Stem cells (Dayton, Ohio) (2020-08-08)
Dong-Yeop Shin, Xinxin Huang, Chang-Hyun Gil, Arafat Aljoufi, James Ropa, Hal E Broxmeyer
摘要

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.

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Sigma-Aldrich
MS5-hDLL1 Stromal Cell Line, The MS5-mDLL1 stromal cell line is used in a serum-free artificial thymic organoid (ATO) system to generate mature T-cells from human hematopoietic stem and progenitor cells.
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