4.6 Article

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

Journal

JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 6, Issue 3, Pages 239-254

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2020.11.017

Keywords

cardiac spheroids; cardiomyocyte; cell transplantation; heart failure; human iPS cells

Funding

  1. Highway Program for Realization of Regenerative Medicine from the Japan Agency for Medical Research and Development [17bm054006h0007]
  2. Research Project for Practical Applications of Regenerative Medicine from the Japan Agency for Medical Research and Development [17bk010462h0001]
  3. Ministry of Education, Culture, Sports, Science and Technology [15K09098, 16K09507, 19H03660, 17H05067, 18K15903]
  4. Grants-in-Aid for Scientific Research [19H03660, 17H05067, 16K09507, 18K15903, 15K09098] Funding Source: KAKEN

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The severe shortage of donor hearts hampers cardiac transplantation, leading to high expectations for cardiac regenerative therapies. hiPSC-derived cardiomyocytes offer a realistic cell source for heart recovery. Avoiding teratoma formation and scaling up cardiomyocyte culture are essential for clinical applications. Spheroids and gelatin hydrogel combination has shown success in recovering reduced ejection fraction, and a feasible transplantation strategy for regenerative cardiomyocytes has been established in this study.
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. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

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