The importance of hypoxia and extra physiologic oxygen shock/stress for collection and processing of stem and progenitor cells to understand true physiology/pathology of these cells ex vivo.
The importance of hypoxia and extra physiologic oxygen shock/stress for collection and processing of stem and progenitor cells to understand true physiology/pathology of these cells ex vivo.
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DOI：
10.1097/moh.0000000000000144
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发表时间：
2015-07
影响因子：
3.2
通讯作者：
Mantel C
中科院分区：
文献类型：
--
作者：
Broxmeyer HE;O'Leary HA;Huang X;Mantel C
造血干细胞 (HSC) 和祖细胞 (HPC) 存在于体内低氧（氧 (O2) 张力降低）环境中。我们回顾了有关 HSC 和 HPC 在低氧和常氧（环境空气）条件下生长的文献，重点是我们最近的工作，证明了通过称为额外生理氧冲击/应激 (EPHOSS) 的现象在环境空气中收集和处理细胞的有害影响，并且我们描述了抵消 EPHOSS 以增强 HSC 收集的方法。在环境空气中收集和处理骨髓 (BM) 和脐带血 (CB) 细胞会导致 HSC 快速分化和损失，同时 HPC 增加。这种明显不可逆的 EPHOSS 现象是由 p53-亲环蛋白 D - 线粒体通透性转换孔 (MPTP) 轴介导的线粒体 ROS 增加所致，并涉及 hif-1α 和 miR210。可以通过在降低的 (3%) O2 中或在存在环孢菌素 A (CSA) 的环境空气中收集和处理细胞来减轻 EPHOSS，环孢菌素 A (CSA) 会影响 MPTP，从而增加 HSC 收集。我们最近的发现可能有利于造血细胞移植的 HSC 收集，并可能有利于加强其他干细胞类型的收集。当离体细胞分析用于个性化医疗时，应考虑 EPHOSS，因为离体细胞的代谢及其对靶向药物治疗的反应可能无法模拟体内发生的情况。
Hematopoietic stem (HSCs), and progenitor (HPCs) cells reside in a hypoxic (lowered oxygen (O2) tension) environment, in vivo. We review literature on growth of HSCs and HPCs under hypoxic and normoxic (ambient air) conditions with a focus on our recent work demonstrating the detrimental effects of collecting and processing cells in ambient air through a phenomenon termed Extra Physiologic Oxygen Shock/Stress (EPHOSS), and we describe means to counteract EPHOSS for enhanced collection of HSCs. Collection and processing of bone marrow (BM) and cord blood (CB) cells in ambient air causes rapid differentiation, and loss of HSCs, with increases in HPCs. This apparently irreversible EPHOSS phenomenon results from increased mitochondrial ROS, mediated by a p53-Cyclophilin D – mitochondrial permeability transition pore (MPTP) axis, and involves hif-1α and miR210. EPHOSS can be mitigated by collecting and processing cells in lowered (3%) O2, or in ambient air in the presence of, cyclosporine A (CSA) which effects the MPTP, resulting in increased HSC collections. Our recent findings may be advantageous for HSC collection for hematopoietic cell transplantation, and likely for enhanced collection of other stem cells types. EPHOSS should be considered when ex-vivo cell analysis is utilized for personalized medicine, since metabolism of cells and their response to targeted drug treatment ex-vivo may not mimic what occurs in vivo.