| Literature DB >> 26073944 |
Charlie R Mantel1, Heather A O'Leary1, Brahmananda R Chitteti2, XinXin Huang1, Scott Cooper1, Giao Hangoc1, Nickolay Brustovetsky3, Edward F Srour4, Man Ryul Lee5, Steven Messina-Graham1, David M Haas6, Nadia Falah6, Reuben Kapur7, Louis M Pelus1, Nabeel Bardeesy8, Julien Fitamant8, Mircea Ivan9, Kye-Seong Kim10, Hal E Broxmeyer11.
Abstract
Hematopoietic stem cells (HSCs) reside in hypoxic niches within bone marrow and cord blood. Yet, essentially all HSC studies have been performed with cells isolated and processed in non-physiologic ambient air. By collecting and manipulating bone marrow and cord blood in native conditions of hypoxia, we demonstrate that brief exposure to ambient oxygen decreases recovery of long-term repopulating HSCs and increases progenitor cells, a phenomenon we term extraphysiologic oxygen shock/stress (EPHOSS). Thus, true numbers of HSCs in the bone marrow and cord blood are routinely underestimated. We linked ROS production and induction of the mitochondrial permeability transition pore (MPTP) via cyclophilin D and p53 as mechanisms of EPHOSS. The MPTP inhibitor cyclosporin A protects mouse bone marrow and human cord blood HSCs from EPHOSS during collection in air, resulting in increased recovery of transplantable HSCs. Mitigating EPHOSS during cell collection and processing by pharmacological means may be clinically advantageous for transplantation.Entities:
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Year: 2015 PMID： 26073944 PMCID： PMC4480616 DOI： 10.1016/j.cell.2015.04.054
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582