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Road to Heart Regeneration with Induced Pluripotent Stem Cells

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Liver, Lung and Heart Regeneration

Part of the book series: Stem Cells in Clinical Applications ((SCCA))

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Abstract

Restoration of cardiac function is the most desirable treatment of severe heart failure. However, effective regenerative therapy for the lost cardiomyocytes is currently an unmet medical need. Induced pluripotent stem cells (iPSCs) are the ideal cell source for regenerative cardiomyocytes, because they can be reprogrammed from patient cells, enabling autologous transplantation. However, the clinical application of iPSC-derived cardiomyocytes is hampered by several roadblocks. The quality of iPSCs must be guaranteed for clinical applications. Although the protocols to differentiate iPSCs to cardiomyocytes have been improved, it remains a substantial challenge to acquire a large amount of iPSC-derived cardiomyocytes. Mass floating cell culture is an effective system to solve this problem; however, the remaining undifferentiated stem cells are the critical issue. The most important step for clinical application is the purification of cardiomyocytes to avoid tumor formation after transplantation, and the quality of regenerative cardiomyocytes must also be controlled. The phenotype of cardiomyocytes is normally infant-type immediately after differentiation, comprising nodal, atrial, and ventricular cardiomyocytes. In addition, the transplantation strategies to support cell engraftment are essential for cell therapies. Co-transplantation with biodegradable materials such as fibrin, collagen, and gelatin may be helpful to improve graft survival. Acute and chronic immunological rejection should be well controlled with appropriate immunosuppressive therapies. Safety issues of transplanted cardiomyocytes, such as arrhythmia, teratoma formation, and side effects of immunosuppressive therapies, are also very important. These fundamental issues must be solved to move toward clinical application, with the ultimate goal of cardiac regenerative therapies with iPSCs.

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Acknowledgements

The present work was supported by the Highway Program for Realization of Regenerative Medicine from Japan Science and Technology Agency (to K.F.).

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Authors and Affiliations

  1. Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo, 160-8582, Japan

    Jun Fujita, Shugo Tohyama, Kazuaki Nakajima, Tomohisa Seki, Hideaki Kanazawa & Keiichi Fukuda

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  1. Jun Fujita
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  2. Shugo Tohyama
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  3. Kazuaki Nakajima
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  4. Tomohisa Seki
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  5. Hideaki Kanazawa
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  6. Keiichi Fukuda
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Corresponding author

Correspondence to Jun Fujita .

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Editors and Affiliations

  1. Laboratory of Stem Cell Research & Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam

    Phuc Van Pham

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Fujita, J., Tohyama, S., Nakajima, K., Seki, T., Kanazawa, H., Fukuda, K. (2017). Road to Heart Regeneration with Induced Pluripotent Stem Cells. In: Pham, P. (eds) Liver, Lung and Heart Regeneration. Stem Cells in Clinical Applications. Springer, Cham. https://doi.org/10.1007/978-3-319-46693-4_8

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