Physioxia enhances T cell development ex vivo from human hematopoietic stem and progenitor cells,STEM CELLS

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Physioxia enhances T cell development ex vivo from human hematopoietic stem and progenitor cells
STEM CELLS ( IF 4.0 ) Pub Date : 2020-08-15 , DOI: 10.1002/stem.3259
Dong-Yeop Shin _{1,

2} , Xinxin Huang ₃ , Chang-Hyun Gil ₄ , Arafat Aljoufi ₁ , James Ropa ₁ , Hal E Broxmeyer ₁

Affiliation

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.

中文翻译：

Physioxia 增强了来自人类造血干细胞和祖细胞的 T 细胞体外发育

了解造血干 (HSC) 和祖细胞 (HPC) 的生理性 T 细胞发育对于改进造血细胞移植 (HCT) 和新兴 T 细胞疗法的发展至关重要。胸腺生态位中的因素，包括 Notch 1 受体配体，通过体外 T 细胞发育指导 HSC 和 HPC。我们报告说，生理相关的氧浓度（5% O2，生理氧）是一种重要的环境胸腺因子，可促进脐血 CD34+ 细胞在无血清和无饲养层培养系统中分化为祖 T（proT）细胞。强效还原剂和抗氧化剂抗坏血酸可增强这种效果。与环境空气相比，悬浮培养中的人 CD34+ 细胞衍生的 proT 细胞在人工胸腺类器官 (ATO) 培养系统中成熟为 CD3+ T 细胞时，在有氧条件下更有效。低氧张力作为 HSC 定型和 HPC 向无饲养层培养系统中的 proT 细胞分化以及在 ATO 中进一步成熟为 T 细胞的正调节器。在生理氧中培养 HSCs/HPCs 是体外有效祖 T 细胞和成熟 T 细胞产生的增强方法，未来可能用于 HCT 和 T 细胞免疫疗法。

更新日期：2020-08-15

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