Reactive oxygen species and stem/progenitor cells

Abstract

Stem cells are defined as cells that have the capacity of self-renewal, multipotency/pluripotency, and clonality. The bone marrow (BM) microenvironment, also termed the stem cell niche, regulates self-renewal, differentiation, survival, migration, and proliferation of stem/progenitor cells as well as their mobilization involved in neovascularization and tissue repair. Reactive oxygen species (ROS) play an important role in regulating stem and progenitor cell function. A low level of endogenous ROS is involved in maintaining the quiescence of hematopoietic stem cells (HSCs), whereas a higher level of ROS 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 BM microenvironment, which in turn promotes oxygen consumption and HIF-1α expression 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 inflammatory and oxidative microenvironment, which induces cell damage and apoptosis of stem and progenitor cells. Understanding the molecular mechanisms of how ROS regulate function of stem and progenitor cells and their niche in physiological and pathological conditions will lead to the development of novel therapeutic strategies.