You are hereNovember 2, 2020 | Haematopoetic Stem Cells
Lower Oxygen Levels Provide a Boost For T-Cell Therapies
Review of “Physioxia enhances T‐cell development ex vivo from human hematopoietic stem and progenitor cells” from STEM CELLS by Stuart P. Atkinson
T lymphocytes originate from bone marrow resident stem cells; however, these all-important immune cells undergo differentiation and maturation in the thymus gland. As oxygen concentrations in the thymus  can fall below those observed in the bone marrow or spleen [2-4], researchers led by Hal E. Broxmeyer (Indiana University School of Medicine, Indianapolis, IN, USA) recently sought to explore the influence of physiologically relevant oxygen concentrations (≤5% O2, or “physioxia”) on T lymphocyte commitment and development ex vivo. The improved generation of T lymphocytes may impact patients undergoing hematopoietic cell transplantation and the development of emerging T‐cell therapies.
In their new STEM CELLS article , Shin et al. now reports that the culture of hematopoietic stem/progenitor cells under conditions of physioxia to mimic the thymic niche and in the presence of the antioxidant ascorbic acid  promotes the enhanced production of T lymphocyte progenitor cells and the maturation of T lymphocytes in an ex vivo artificial thymic organoid culture system. Can lower oxygen levels provide a boost for T-lymphocyte-based therapeutic approaches?
Using a previously described non‐xenogeneic serum‐free and feeder‐free suspension culture system , the Broxmeyer team established that a physiologically relevant oxygen concentration significantly improved cord blood-derived hematopoietic stem cell commitment and hematopoietic progenitor cell differentiation into T lymphocyte progenitor cells over two weeks. The authors further enhanced hematopoietic progenitor cell differentiation by adding ascorbic acid (vitamin C), a potent reducing and antioxidant agent.
Encouragingly, the team then discovered that the presence of a physiologically relevant oxygen concentration and ascorbic acid improved the subsequent maturation of T lymphocyte progenitor cells into CD3+ T lymphocytes within artificial thymic organoids formed in the presence of mouse feeder cells over four weeks .
This exciting study represents the first description of the positive effect of a physiologically relevant oxygen concentration on T lymphocyte differentiation and maturation in ex vivo culture systems. Notably, the authors state that these stem cell culture refinements can be easily translated to good manufacturing practice-scale, clinics for patients undergoing hematopoietic cell transplantation, and the development of emerging T‐cell therapies.
For more on how lower oxygen levels may provide a boost for T-lymphocyte-based therapeutic approaches, stay tuned to the Stem Cells Portal!
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- Shin D-Y, Huang X, Gil C-H, et al., Physioxia enhances T-cell development ex vivo from human hematopoietic stem and progenitor cells. STEM CELLS 2020;38:1454-1466.
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