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Direct Cardiac Reprogramming as a Novel Therapeutic Strategy for Treatment of Myocardial Infarction

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Cardiac Gene Therapy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1521))

Abstract

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds great promise as a novel therapy for the treatment of heart failure, a common and morbid disease that is usually caused by irreversible loss of functional cardiomyocytes (CMs). Recently, we and others showed that in a murine model of acute myocardial infarction, delivery of three transcription factors, Gata4, Mef2c, and Tbx5 converted endogenous cardiac fibroblasts into functional iCMs. These iCMs integrated electrically and mechanically with surrounding myocardium, resulting in a reduction in scar size and an improvement in heart function. Our findings suggest that iCM reprogramming may be a means of regenerating functional CMs in vivo for patients with heart disease. However, because relatively little is known about the factors that regulate iCM reprogramming, the applicability of iCM reprogramming is currently limited to the experimental settings in which it has been attempted. Specific hurdles include the relatively low conversion rate of iCMs and the need for reprogramming to occur in the context of acute injury. Therefore, before this treatment can become a viable therapy for human heart disease, the optimal condition for efficient iCM generation must be determined. Here, we provide a detailed protocol for both in vitro and in vivo iCM generation that has been optimized so far in our lab. We hope that this protocol will lay a foundation for future further improvement of iCM generation and provide a platform for mechanistic studies.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, McAllister Heart Institute, University of North Carolina, 3340B Medical Bioresearch Building, 111 Mason Farm Rd, Chapel Hill, NC, 27599, USA

    Hong Ma, Li Wang, Jiandong Liu & Li Qian Ph.D.

Authors
  1. Hong Ma
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  2. Li Wang
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  3. Jiandong Liu
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  4. Li Qian Ph.D.
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Corresponding author

Correspondence to Li Qian Ph.D. .

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Editors and Affiliations

  1. Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA

    Kiyotake Ishikawa

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Ma, H., Wang, L., Liu, J., Qian, L. (2017). Direct Cardiac Reprogramming as a Novel Therapeutic Strategy for Treatment of Myocardial Infarction. In: Ishikawa, K. (eds) Cardiac Gene Therapy. Methods in Molecular Biology, vol 1521. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6588-5_5

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  • DOI: https://doi.org/10.1007/978-1-4939-6588-5_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6586-1

  • Online ISBN: 978-1-4939-6588-5

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