Redox regulation of stem/progenitor cells and bone marrow niche

Norifumi Urao, Masuko Ushio-Fukai

Research output: Contribution to journalReview articlepeer-review

104 Scopus citations

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 (H2O2), play important roles in regulating stem and progenitor cell functions in various physiologic and pathologic responses. The low level of H2O 2 in quiescent hematopoietic stem cells (HSCs) contributes to maintaining 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 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.

Original languageEnglish (US)
Pages (from-to)26-39
Number of pages14
JournalFree Radical Biology and Medicine
Volume54
DOIs
StatePublished - Jan 2013

Keywords

  • Bone marrow
  • Free radicals
  • Hypoxia
  • NADPH oxidase
  • Niche
  • Progenitor cell
  • Reactive oxygen species
  • Stem cell

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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