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Cell-based gene therapy for the prevention and treatment of cardiac dysfunction

Nature Clinical Practice Cardiovascular Medicine volume 4, pages S83–S88 (2007)Cite this article

Abstract

A substantial need exists for new treatments to prevent and treat cardiac dysfunction. In the 1990s, there was great hope for gene therapy in this regard. Since that time, the focus has switched to cell therapy—in particular, therapy—with the aim of inducing myocardial regeneration. Individually, gene and cell therapies still have substantial promise. Ultimately, however, the convergence of both techniques might be necessary to achieve improvements in cardiac function and more successful clinical outcomes in patients with cardiac dysfunction. This approach has already been adopted for treatment of malignancies. Several gene products are currently being studied, including growth factors and chemokines that can modulate the survival and function of cardiac myocytes following an ischemic event and influence remodeling of the left ventricle. However, several issues remain, including the optimization and characterization of cell types, selection of vectors for gene transfer, and identification of appropriate strategies for delivery. Here, we review the potential and need for cell-based gene therapy for the prevention and treatment of cardiac dysfunction and attempt to discuss the unresolved issues.

Key Points

  • Studies of gene therapy for the treatment of ischemia and cardiac dysfunction have yielded numerous potential targets that have, so far, had limited clinical success

  • Stem-cell-based therapies for improving cardiac function at the time of acute myocardial infarction have, thus far, been shown to be safe and have modest benefits on cardiac function

  • The improvements in cardiac function are independent of myocardial regeneration

  • Molecular signals, such as stem cell homing factors, are transiently expressed by the heart following myocardial infarction and absent in hearts weeks to months after myocardial infarction

  • Combining stem cell therapy with gene therapy is a viable strategy for augmenting the effects of cell therapy and targeting pathways of interest for gene therapy

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Figure 1: Percentage increase in the shortening fraction following either direct injection or IV infusion of different committed or stem cell populations immediately following or 1 day after, respectively, ligation of the left anterior descending artery
Figure 2: Schematic diagram of potential gene products of interest for cell-based gene therapy for treatment of acute myocardial infarction and chronic heart failure

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Author notes

  1. NE3, Departments of Cardiovascular Medicine and Cell Biology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA pennm@ccf.org

Authors and Affiliations

  1. MS Penn is Director of the Bakken Heart–Brain Institute in the Departments of Cardiovascular Medicine and Cell Biology at the Cleveland Clinic Foundation, Cleveland, OH, USA.,

    Marc S Penn

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  1. Marc S Penn
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Competing interests

Marc S Penn declared that he is named as a co-inventor on pending patents filed by the Cleveland Clinic Foundation that relate to the use of stem cell homing factors for the treatment of acute myocardial infarction and heart failure. He has received research funds from the following organisations: American Heart Association, Athersys Inc., Becton Dickinson Inc., Cell Targeting Inc., and the NIH (National Institutes of Health). He has also received licensing fees from Bioheart Inc.

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Penn, M. Cell-based gene therapy for the prevention and treatment of cardiac dysfunction. Nat Rev Cardiol 4 (Suppl 1), S83–S88 (2007). https://doi.org/10.1038/ncpcardio0733

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