title: Redox regulation of stem/progenitor cells and bone marrow niche.
abstract: Bone marrow (BM)-derived stem and progenitor cell functions including self-renewal, differentiation, survival, migration, proliferation, and mobilization are regulated by unique cell-intrinsic and -extrinsic signals provided by their microenvironment, also termed the "niche." Reactive oxygen species (ROS), especially hydrogen peroxide (H(2)O(2)), play important roles in regulating stem and progenitor cell functions in various physiologic and pathologic responses. The low level of H(2)O(2) in quiescent hematopoietic stem cells (HSCs) contributes to maintaining their "stemness," whereas a higher level of H(2)O(2) 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 hypoxia-inducible factor-1α 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.
authors.affiliation: Department of Pharmacology, Center for Lung and Vascular Biology, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Urao
authors.forename: Masuko
authors.initials: M
authors.lastname: Ushio-Fukai
mesh_terms: D000818:Animals; D001691:Biological Therapy; D001853:Bone Marrow / Q000502:physiology*; D060833:Cellular Microenvironment; D006801:Humans; D007511:Ischemia / Q000503:physiopathology* / Q000628:therapy; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D055153:Stem Cell Niche; D013234:Stem Cells / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases