Journal of Molecular and Cellular Cardiology
Volume 50, Issue 2 , Pages 280-289, February 2011

Paracrine mechanisms of stem cell reparative and regenerative actions in the heart

  • Maria Mirotsou

      Affiliations

    • Department of Medicine, Duke University Medical Center & Mandel Center for Hypertension and Atherosclerosis Research, Durham, NC 27710, USA
  • ,
  • Tilanthi M. Jayawardena

      Affiliations

    • Department of Medicine, Duke University Medical Center & Mandel Center for Hypertension and Atherosclerosis Research, Durham, NC 27710, USA
  • ,
  • Jeffrey Schmeckpeper

      Affiliations

    • Department of Medicine, Duke University Medical Center & Mandel Center for Hypertension and Atherosclerosis Research, Durham, NC 27710, USA
  • ,
  • Massimiliano Gnecchi

      Affiliations

    • Laboratory of Experimental Cardiology for Cell and Molecular Therapy, Fondazione IRCCS Policlinico San Matteo and Department of Heart, Blood and Lung, University of Pavia, Pavia, Italy
  • ,
  • Victor J. Dzau

      Affiliations

    • Department of Medicine, Duke University Medical Center & Mandel Center for Hypertension and Atherosclerosis Research, Durham, NC 27710, USA
    • Corresponding Author InformationCorresponding author. Office of the Chancellor, Duke University, Medical Center and Health System, DUMC 3701, Durham, NC 27710, USA. Tel.: +1 919 684 2555; fax: +1 919 681 7020.

Received 18 June 2010; received in revised form 2 August 2010; accepted 3 August 2010. published online 20 August 2010.

Abstract 

Stem cells play an important role in restoring cardiac function in the damaged heart. In order to mediate repair, stem cells need to replace injured tissue by differentiating into specialized cardiac cell lineages and/or manipulating the cell and molecular mechanisms governing repair. Despite early reports describing engraftment and successful regeneration of cardiac tissue in animal models of heart failure, these events appear to be infrequent and yield too few new cardiomyocytes to account for the degree of improved cardiac function observed. Instead, mounting evidence suggests that stem cell mediated repair takes place via the release of paracrine factors into the surrounding tissue that subsequently direct a number of restorative processes including myocardial protection, neovascularization, cardiac remodeling, and differentiation. The potential for diverse stem cell populations to moderate many of the same processes as well as key paracrine factors and molecular pathways involved in stem cell‐mediated cardiac repair will be discussed in this review. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

Research highlights

► Stem cell secreted soluble factors improve overall cardiac function in the damaged myocardium. ► Healing processes include protection, neovascularization, differentiation, and remodeling. ► Adult stem cells that mediate cytoprotective effects include MSCs, BM-MNCs, EPCs and CPCs. ► Stem cell mediated paracrine effects can be enhanced by ex vivo and genetic modification. ► Though challenges remain, paracrine factor remains a promising therapy for cardiac repair.

Keywords: Paracrine factors, Stem cells, Cardiac repair, Cardiac regeneration

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PII: S0022-2828(10)00292-0

doi:10.1016/j.yjmcc.2010.08.005

Journal of Molecular and Cellular Cardiology
Volume 50, Issue 2 , Pages 280-289, February 2011