Physioxia enhances T-cell development ex vivo from human hematopoietic stem and progenitor cells
dc.contributor.author | Shin, Dong-Yeop | |
dc.contributor.author | Huang, Xinxin | |
dc.contributor.author | Gil, Chang-Hyun | |
dc.contributor.author | Aljoufi, Arafat | |
dc.contributor.author | Ropa, James | |
dc.contributor.author | Broxmeyer, Hal E. | |
dc.contributor.department | Microbiology and Immunology, School of Medicine | en_US |
dc.date.accessioned | 2022-05-13T12:14:18Z | |
dc.date.available | 2022-05-13T12:14:18Z | |
dc.date.issued | 2020-11 | |
dc.description.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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Shin 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.3259 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/28992 | |
dc.language.iso | en_US | en_US |
dc.publisher | Nova Science | en_US |
dc.relation.isversionof | 10.1002/stem.3259 | en_US |
dc.relation.journal | Stem Cells | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Cord blood | en_US |
dc.subject | Differentiation | en_US |
dc.subject | Hematopoietic stem and progenitor cells | en_US |
dc.subject | Hypoxia | en_US |
dc.subject | Physioxia | en_US |
dc.subject | Progenitor T cells | en_US |
dc.subject | T cells | en_US |
dc.title | Physioxia enhances T-cell development ex vivo from human hematopoietic stem and progenitor cells | en_US |
dc.type | Article | en_US |