Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues

To establish a protocol to prepare and transplant clinical-grade human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) and to evaluate the therapeutic potential in an animal myocardial infarction (MI) model. We simultaneously differentiated clinical-grade hiPSCs into cardiovasc...

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Bibliographic Details
Published in:JTCVS open 2021-12, Vol.8, p.359-374
Main Authors: Osada, Hiroaki, Kawatou, Masahide, Fujita, Daiki, Tabata, Yasuhiko, Minatoya, Kenji, Yamashita, Jun K., Masumoto, Hidetoshi
Format: Article
Language:English
Subjects:
Adult: Coronary: Basic Science
cardiac regenerative therapy
heart failure
induced pluripotent stem cell
transplantation
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Summary:To establish a protocol to prepare and transplant clinical-grade human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) and to evaluate the therapeutic potential in an animal myocardial infarction (MI) model. We simultaneously differentiated clinical-grade hiPSCs into cardiovascular cell lineages with or without the administration of canonical Wnt inhibitors, generated 5- layer cell sheets with insertion of gelatin hydrogel microspheres (GHMs) (HiCTs), and transplanted them onto an athymic rat MI model. Cardiac function was evaluated by echocardiography and cardiac magnetic resonance imaging and compared with that in animals with sham and transplantation of 5-layer cell sheets without GHMs. Graft survival, ventricular remodeling, and neovascularization were evaluated histopathologically. The administration of Wnt inhibitors significantly promoted cardiomyocyte (CM) (P 
ISSN:2666-2736
2666-2736
DOI:10.1016/j.xjon.2021.09.038