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Redox Regulation of Stem/Progenitor Cells and Bone Marrow Niche

journal contribution
posted on 26.11.2013, 00:00 authored by Norifumi Urao, Masuko Ushio-Fukai
Bone marrow (BM)-derived stem and progenitor cell functions including self-renewal, differentiation, survival, migration, proliferation and mobilization are regulated by unique cell-intrinsic signals and -extrinsic signals provided by their microenvironment, also termed the ‘niche’. Reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), play important roles in regulating stem and progenitor cell function in various physiologic and pathologic responses. The low level of H2O2 in quiescent hematopoietic stem cells (HSCs) contributes to maintain their stemness, whereas a higher level of H2O2 within HSCs or their niche promotes differentiation, proliferation, migration, and survival of HSCs or stem/progenitor cells. Major sources of ROS are NADPH oxidase and mitochondria. In response to ischemic injury, ROS derived from NADPH oxidase are increased in the BM microenvironment, which is required for hypoxia and HIF1α expression and expansion throughout the BM. This, in turn, promotes progenitor cell expansion and mobilization from BM, leading to reparative neovascularization and tissue repair. In pathophysiological states such as aging, atherosclerosis, heart failure, hypertension and diabetes, excess amounts of ROS create an inflammatory and oxidative microenvironment, which induces cell damage and apoptosis of stem and progenitor cells. Understanding the molecular mechanisms of how ROS regulate the functions of stem and progenitor cells and their niche in physiological and pathological conditions will lead to the development of novel therapeutic strategies.


This work was supported by funds from National Institutes of Health (NIH) R01 Heart and Lung (HL)077524, HL077524-S1 (to M.U.-F.), American Heart Association (AHA) National Center Research Program (NCRP) Innovative Research Grant 0970336N (to M.U.-F), AHA Post-doctoral Fellowship 09POST2250151 (to N.U.), and AHA Scientist Development Grant 12SDG12060100 (to N.U.).


Publisher Statement

NOTICE: This is the author’s version of a work that was accepted for publication in Free Radical Biology and Medicine. Changes resulting from the publisFree Radical Biology and Medicinehing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Free Radical Biology and Medicine, Vol 54, (2013) DOI: 10.1016/j.freeradbiomed.2012.10.532







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