Redox regulation of regeneration of infarcted heart with stem cells: Role of micro RNA

Mobilization and homing of the hematopoietic stem cells appear to be regulated by mechanism involving redox cycling. Stem cells are localized inside bone marrow in a strictly hypoxic environment and must move to the injury site that is subjected to oxidative environment. Cytokines and adhesion molecules control stem cell mobilization through a redox-regulated process. The major hitch in stem cell therapy includes the life of the stem cells after the stem cell therapy; most cells do not survive beyond 24 to 72 hours. Sudden exposure of the stem cells from the hypoxic meleu into the oxidative environment likely to cause severe injury to the cells. FoxO-SirT network appears to be intimately involved in redox-regulated stem cell homeostasis while their differentiation process is regulated by redox factor protein-1 (Ref-1). Lack of oxygen [hypoxia], specifically controlled hypoxia can stimulate the growth of the stem cells in their niche and HIF-1a plays a significant role in their maintenance and homing mechanism. Recently, resveratrol, a polyphenolic phytoalexin prolonged the survival of the stem cells as evidenced by active proliferation and differention of the cells even after four months of cell therapy. The enhancement of stem cell survival was shown to be due to the ability of resveratrol to maintain a reduced tissue environment by over-expressing Nrf2 and Ref-1 in rat heart up to six months resulting in an enhancement of the regeneration of the adult cardiac stem cells as evidenced by increased cell survival and differentiation leading to improved cardiac function. Expression of SDF and myosin conclusively demonstrated homing of stem cells in the infracted myocardium, its regeneration leading to improvement of cardiac function.