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Stem cell death and survival in heart regeneration and repair

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Abstract

Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

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Acknowledgments

We thank Denislam Zaripov for skillful art drawing. E.A. was supported by the National Heart, Lung, and Blood Institute (NIH/NHLBI), grant SP0012613. A.S. and A.K. were supported by the European Social Fund under National Integrated Programme Biotechnology & Biopharmacy, Grant VP1-3.1-SMM-08-K01-005.

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Authors and Affiliations

  1. Feinberg School of Medicine, Feinberg Cardiovascular Research Institute, Northwestern University, 303 E. Chicago Ave., Tarry 14–725, Chicago, IL, 60611, USA

    Eltyeb Abdelwahid

  2. Department of Molecular Cell Biology, Vilnius University Institute of Biochemistry, Vilnius, Lithuania

    Audrone Kalvelyte & Aurimas Stulpinas

  3. Cell Therapy and Biotechnology in Regenerative Medicine Research Group, Pequeno Príncipe Faculty, Pelé Pequeno Príncipe Institute, Curitiba, Paraná, 80250-200, Brazil

    Katherine Athayde Teixeira de Carvalho

  4. Experimental Laboratory of Institute of Biological and Health Sciences of Pontifical Catholic University of Parana, Curitiba, Paraná, 80215-901, Brazil

    Luiz Cesar Guarita-Souza

  5. National Heart and Lung Institute, Imperial College London, Imperial Centre for Experimental and Translational Medicine, Du Cane Road, London, W12 0NN, UK

    Gabor Foldes

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  1. Eltyeb Abdelwahid
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Abdelwahid, E., Kalvelyte, A., Stulpinas, A. et al. Stem cell death and survival in heart regeneration and repair. Apoptosis 21, 252–268 (2016). https://doi.org/10.1007/s10495-015-1203-4

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