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Harnessing the Induction of Cardiomyocyte Proliferation for Cardiac Regenerative Medicine

  • Regenerative Medicine and Stem-cell Therapy (S Wu and P Hsieh, Section Editors)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

Adult human cardiomyocytes are terminally differentiated and have limited capacity for cell division. Hence, they are not naturally replaced following ischemic injury to the heart. As such, cardiac function is often permanently compromised after an event such as myocardial infarction. In recent years, investigators have focused intensively on ways to reactivate cardiomyocyte mitotic activity in both in vitro cell culture systems and in vivo animal models. In parallel, advances in stem cell biology have allowed for the mass production of patient-specific human cardiomyocytes from human-induced pluripotent stem cells. These cells can be produced via chemically defined differentiation of human pluripotent stem cells in a matter of weeks and could theoretically be utilized directly for therapeutic purposes to replace damaged myocardium. However, stem cell-derived cardiomyocytes, like their adult counterparts, are post-mitotic and incapable of large-scale expansion after reaching a certain stage of in vitro differentiation. Due to this shared characteristic, these stem cell-derived cardiomyocytes may provide a platform for studying genes, pathways, and small molecules that induce cell cycle reentry and proliferation of human cardiomyocytes. Ultimately, the discovery of novel mechanisms or pathways to induce human cardiomyocyte proliferation should improve our ability to regenerate adult cardiomyocytes and help restore cardiac function following injury.

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Acknowledgments

This work is supported by a National Science Foundation Graduate Research Fellowship (to A. S.) and an NIH Director’s Pioneer Award, NIH/NHLBI U01 HL099067, American Heart Association Grant-in-Aid (to S.M.W.).

Compliance with Ethics Guidelines

Conflict of Interest

Arun Sharma reports grants from National Science Foundation and personal fees from Stanford University.

Yuan Zhang declares no potential conflicts of interest.

Sean M. Wu reports grants from National Institutes of Health and American Heart Association and personal fees from Stanford University and Silver Creek Pharmaceutical. Dr. Wu is a section editor for Current Treatment Options in Cardiovascular Medicine.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, 94305, USA

    Arun Sharma BS, Yuan Zhang & Sean M. Wu MD PhD

  2. Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Arun Sharma BS, Yuan Zhang & Sean M. Wu MD PhD

  3. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Sean M. Wu MD PhD

  4. G1120A Lokey Stem Cell Building, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA

    Sean M. Wu MD PhD

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  1. Arun Sharma BS
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Correspondence to Sean M. Wu MD PhD.

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This article is part of the Topical Collection on Regenerative Medicine and Stem-cell Therapy

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Sharma, A., Zhang, Y. & Wu, S.M. Harnessing the Induction of Cardiomyocyte Proliferation for Cardiac Regenerative Medicine. Curr Treat Options Cardio Med 17, 45 (2015). https://doi.org/10.1007/s11936-015-0404-z

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