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Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock

Title
Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock
Author
김계성
Keywords
MITOCHONDRIAL PERMEABILITY TRANSITION; ADENINE-NUCLEOTIDE TRANSLOCASE; UMBILICAL-CORD BLOOD; CYCLOSPORINE-A; OXIDATIVE STRESS; PROGENITOR CELLS; BONE-MARROW; INNER-MEMBRANE; CYCLOPHILIN-D; ISCHEMIA/REPERFUSION INJURY
Issue Date
2015-06
Publisher
CELL PRESS
Citation
CELL, v. 161, NO 7, Page. 1553-1565
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.
URI
http://www.sciencedirect.com/science/article/pii/S0092867415005747http://hdl.handle.net/20.500.11754/25608
ISSN
0092-8674; 1097-4172
DOI
10.1016/j.cell.2015.04.054
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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