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Clinical Application of iPSC-Derived Cardiomyocytes in Patients with Advanced Heart Failure

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Advanced Technologies in Cardiovascular Bioengineering

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Abstract

Restoration of damaged cardiac tissues via supplementation with functional cardiomyocytes is an ideal medical treatment for advanced heart failure. Because human induced pluripotent stem cells (hiPSCs) can theoretically reproduce all kinds of cells from the patients themselves, their derivatives are expected to aid in the repair or replacement in these dysfunctional tissues. To improve cardiac function, a large number of cardiomyocytes must be prepared and transplanted into the damaged heart. Thus, large-scale cell culture systems are necessary for both clinical and industrial applications. In addition, the development of tumors, produced by any residual undifferentiated stem cells, should be avoided to prevent their deleterious effects. This means that efficient differentiation and purification methods are critical to the clinical application of hiPSCs. Transplantation strategies are also critical to the efficient retention and engraftment of cardiomyocytes and should be designed to minimize unwanted immunogenic effects preventing inflammation and immunological rejection and facilitating long-term engraftment. Arrhythmogenicity is also often described in middle-large animal models making this a critical functional issue that should be addressed before moving into human patients. Continued investigation and application of findings is sure to facilitate the successful clinical application of hiPSC-derived cardiomyocytes in the treatment of advanced heart failure.

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Acknowledgements

This work was supported by a Grant-in-Aid of Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (19H03660 [to Dr. Fujita]). Drs. Fujita, Tohyama, Kanazawa, and Fukuda all retain patents related to this work. Drs. Fujita, Tohyama, Kanazawa, and Fukuda own equity in Heartseed, Inc. Dr. Tohyama is an advisor of Heartseed, Inc. and Dr. Fukuda is the co-founder and CEO of Heartseed, Inc., and receives a salary from Heartseed, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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Authors and Affiliations

  1. Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

    Jun Fujita, Shugo Tohyama, Hideaki Kanazawa, Yoshikazu Kishino, Marina Okada, Sho Tanosaki, Shota Someya & Keiichi Fukuda

  2. Endowed Course for Severe Heart Failure Treatment II, Keio University School of Medicine, Tokyo, Japan

    Jun Fujita

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  1. Jun Fujita
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Correspondence to Jun Fujita .

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  1. Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA

    Jianyi Zhang

  2. Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Vahid Serpooshan

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Fujita, J. et al. (2022). Clinical Application of iPSC-Derived Cardiomyocytes in Patients with Advanced Heart Failure. In: Zhang, J., Serpooshan, V. (eds) Advanced Technologies in Cardiovascular Bioengineering. Springer, Cham. https://doi.org/10.1007/978-3-030-86140-7_16

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