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Mesenchymal Stem Cells for Cardiac Therapy: Practical Challenges and Potential Mechanisms

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Abstract

Cell based treatments for myocardial infarction have demonstrated efficacy in the laboratory and in phase I clinical trials, but the understanding of such therapies remains incomplete. Mesenchymal stem cells (MSCs) are classically defined as maintaining the ability to generate mesenchyme-derived cell types, namely adipocytes, chondrocytes and osteocytes. Recent evidence suggests these cells may in fact harbor much greater potency than originally realized, as several groups have found that MSCs can form cardiac lineage cells in vitro. Additionally, experimental coculture of MSCs with cardiomyocytes appears to improve contractile function of the latter. Bolstered by such findings, several clinical trials have begun to test MSC transplantation for improving post-infarct cardiac function in human patients. The results of these trials have been mixed, underscoring the need to develop a deeper understanding of the underlying stem cell biology. To help synthesize the breadth of studies on the topic, this paper discusses current challenges in the field of MSC cellular therapies for cardiac repair, including methods of cell delivery and the identification of molecular markers that accurately specify the therapeutically relevant mesenchymal cell types. The various possible mechanisms of MSC mediated cardiac improvement, including somatic reprogramming, transdifferentiation, paracrine signaling, and direct electrophysiological coupling are also reviewed. Finally, we consider the traditional cell culture microenvironment, and the promise of cardiac tissue engineering to provide biomimetic in vitro model systems to more faithfully investigate MSC biology, helping to safely and effectively translate exciting discoveries in the laboratory to meaningful therapies in the clinic.

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Acknowledgments

The authors acknowledge financial support by the Mount Sinai Medical Scientist Training Program Grant T32-GM007280 (TJC) and NIH/NHLBI R21-HL095980 (KDC).

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The authors declare no potential conflicts of interest

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Authors and Affiliations

  1. Cardiovascular Cell and Tissue Engineering Laboratory, Cardiovascular Research Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, NY, 10029, USA

    Timothy J. Cashman & Kevin D. Costa

  2. Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1020, New York, NY, 10029, USA

    Valerie Gouon-Evans

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  1. Timothy J. Cashman
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Correspondence to Kevin D. Costa.

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Cashman, T.J., Gouon-Evans, V. & Costa, K.D. Mesenchymal Stem Cells for Cardiac Therapy: Practical Challenges and Potential Mechanisms. Stem Cell Rev and Rep 9, 254–265 (2013). https://doi.org/10.1007/s12015-012-9375-6

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