Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model.
Circulation
; 126(11 Suppl 1): S29-37, 2012 Sep 11.
Article
en En
| MEDLINE
| ID: mdl-22965990
ABSTRACT
BACKGROUND:
Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are a promising source of cells for regenerating myocardium. However, several issues, especially the large-scale preparation of hiPS-CMs and elimination of undifferentiated iPS cells, must be resolved before hiPS cells can be used clinically. The cell-sheet technique is one of the useful methods for transplanting large numbers of cells. We hypothesized that hiPS-CM-sheet transplantation would be feasible, safe, and therapeutically effective for the treatment of ischemic cardiomyopathy. METHODS ANDRESULTS:
Human iPS cells were established by infecting human dermal fibroblasts with a retrovirus carrying Oct3/4, Sox2, Klf4, and c-Myc. Cardiomyogenic differentiation was induced by WNT signaling molecules, yielding hiPS-CMs that were almost 90% positive for α-actinin, Nkx2.5, and cardiac troponin T. hiPS-CM sheets were created using thermoresponsive dishes and transplanted over the myocardial infarcts in a porcine model of ischemic cardiomyopathy induced by ameroid constriction of the left anterior descending coronary artery (n=6 for the iPS group receiving sheet transplantation and the sham-operated group; both groups received tacrolimus daily). Transplantation significantly improved cardiac performance and attenuated left ventricular remodeling. hiPS-CMs were detectable 8 weeks after transplantation, but very few survived long term. No teratoma formation was observed in animals that received hiPS-CM sheets.CONCLUSIONS:
The culture system used yields a large number of highly pure hiPS-CMs, and hiPS-CM sheets could improve cardiac function after ischemic cardiomyopathy. This newly developed culture system and the hiPS-CM sheets may provide a basis for the clinical use of hiPS cells in cardiac regeneration therapy.
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Banco de datos:
MEDLINE
Asunto principal:
Técnicas de Cultivo de Célula
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Ingeniería de Tejidos
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Miocitos Cardíacos
/
Células Madre Pluripotentes Inducidas
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Infarto del Miocardio
Tipo de estudio:
Diagnostic_studies
/
Evaluation_studies
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Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article