慶應義塾研究者情報データベース

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• Production of functional cardiomyocytes and cardiac tissue from human induced pluripotent stem cells for regenerative therapy

  Tani H., Tohyama S., Kishino Y., Kanazawa H., Fukuda K.

  Journal of Molecular and Cellular Cardiology （Journal of Molecular and Cellular Cardiology)  164   83 - 91 2022年03月

  ISSN  00222828

  　概要を見る

  The emergence of human induced pluripotent stem cells (hiPSCs) has revealed the potential for curing end-stage heart failure. Indeed, transplantation of hiPSC-derived cardiomyocytes (hiPSC-CMs) may have applications as a replacement for heart transplantation and conventional regenerative therapies. However, there are several challenges that still must be overcome for clinical applications, including large-scale production of hiPSCs and hiPSC-CMs, elimination of residual hiPSCs, purification of hiPSC-CMs, maturation of hiPSC-CMs, efficient engraftment of transplanted hiPSC-CMs, development of an injection device, and avoidance of post-transplant arrhythmia and immunological rejection. Thus, we developed several technologies based on understanding of the metabolic profiles of hiPSCs and hiPSC derivatives. In this review, we outline how to overcome these hurdles to realize the transplantation of hiPSC-CMs in patients with heart failure and introduce cutting-edge findings and perspectives for future regenerative therapy.

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• Intramyocardial Transplantation of Human iPS Cell–Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals

  Kawaguchi S., Soma Y., Nakajima K., Kanazawa H., Tohyama S., Tabei R., Hirano A., Handa N., Yamada Y., Okuda S., Hishikawa S., Teratani T., Kunita S., Kishino Y., Okada M., Tanosaki S., Someya S., Morita Y., Tani H., Kawai Y., Yamazaki M., Ito A., Shibata R., Murohara T., Tabata Y., Kobayashi E., Shimizu H., Fukuda K., Fujita J.

  JACC: Basic to Translational Science （JACC: Basic to Translational Science)  6 （ 3 ） 239 - 254 2021年03月

  ISSN  2452302X

  　概要を見る

  The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.

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• Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells

  Someya S., Tohyama S., Kameda K., Tanosaki S., Morita Y., Sasaki K., Kang M.I., Kishino Y., Okada M., Tani H., Soma Y., Nakajima K., Umei T., Sekine O., Moriwaki T., Kanazawa H., Kobayashi E., Fujita J., Fukuda K.

  iScience （iScience)  24 （ 2 ）  2021年02月

  　概要を見る

  Cell Biology; Metabolomics; Stem Cell Research

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• Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells

  Tanosaki S., Tohyama S., Fujita J., Someya S., Hishiki T., Matsuura T., Nakanishi H., Ohto-Nakanishi T., Akiyama T., Morita Y., Kishino Y., Okada M., Tani H., Soma Y., Nakajima K., Kanazawa H., Sugimoto M., Ko M.S.H., Suematsu M., Fukuda K.

  iScience （iScience)  23 （ 9 ）  2020年09月

  　概要を見る

  Biological Sciences; Cell Biology; Stem Cells Research; Proteomics; Metabolomics; Metabolic Flux Analysis

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• Soft Matrix Promotes Cardiac Reprogramming via Inhibition of YAP/TAZ and Suppression of Fibroblast Signatures

  Kurotsu S., Sadahiro T., Fujita R., Tani H., Yamakawa H., Tamura F., Isomi M., Kojima H., Yamada Y., Abe Y., Murakata Y., Akiyama T., Muraoka N., Harada I., Suzuki T., Fukuda K., Ieda M.

  Stem Cell Reports （Stem Cell Reports)  15 （ 3 ） 612 - 628 2020年09月

  ISSN  22136711

  　概要を見る

  In this article, Ieda and colleagues showed that a soft matrix, which is comparable with native myocardium, efficiently promoted cardiac reprogramming. This soft matrix enhanced cardiac reprogramming via inhibition of integrin, Rho/ROCK, actomyosin, and YAP/TAZ signaling and subsequent suppression of fibroblast programs, which were activated on conventional rigid substrates, thus demonstrating that mechanotransduction plays a critical role in cardiac reprogramming.

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