Shin, Dong-YeopHuang, XinxinGil, Chang-HyunAljoufi, ArafatRopa, JamesBroxmeyer, Hal E.2022-05-132022-05-132020-11Shin DY, Huang X, Gil CH, Aljoufi A, Ropa J, Broxmeyer HE. Physioxia enhances T-cell development ex vivo from human hematopoietic stem and progenitor cells. Stem Cells. 2020;38(11):1454-1466. doi:10.1002/stem.3259https://hdl.handle.net/1805/28992Understanding 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.en-USPublisher PolicyCord bloodDifferentiationHematopoietic stem and progenitor cellsHypoxiaPhysioxiaProgenitor T cellsT cellsArticle