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Stem Cell, MicroRNA and Redox Cycling

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Molecular Defects in Cardiovascular Disease

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Abstract

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 24–72 h. Sudden exposure of the stem cells from the hypoxic melieu into the oxidative environment likely causes 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-1α 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 differentiation of the cells even after 4 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 6 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 stromal cell-derived factor (SDF) and myosin conclusively demonstrated homing of stem cells in the infracted myocardium, its regeneration leading to improvement of cardiac function.

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Acknowledgements

This study was supported in part by NIH HL 34360, HL 33889 and HL 22559.

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Authors and Affiliations

  1. Laboratory of Physiologic Studies, NIAAA, National Institute of Health, Bethesda, MD, USA

    Partha Mukhopadhyay

  2. Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT, USA

    Narasimman Gurusamy & Dipak K. Das

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  1. Partha Mukhopadhyay
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  2. Narasimman Gurusamy
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  3. Dipak K. Das
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Correspondence to Dipak K. Das .

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Editors and Affiliations

  1. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

  2. Jikei University School of Medicine, Shibuya-ku, Ebisu 3-31-6, Tokyo, 150-0013, Japan

    Makoto Nagano

  3. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

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Mukhopadhyay, P., Gurusamy, N., Das, D.K. (2011). Stem Cell, MicroRNA and Redox Cycling. In: Dhalla, N., Nagano, M., Ostadal, B. (eds) Molecular Defects in Cardiovascular Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7130-2_6

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