Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells.

Abstract:

BACKGROUND:Nuclear reprogramming provides an emerging strategy to produce embryo-independent pluripotent stem cells from somatic tissue. Induced pluripotent stem cells (iPS) demonstrate aptitude for de novo cardiac differentiation, yet their potential for heart disease therapy has not been tested. METHODS AND RESULTS:In this study, fibroblasts transduced with human stemness factors OCT3/4, SOX2, KLF4, and c-MYC converted into an embryonic stem cell-like phenotype and demonstrated the ability to spontaneously assimilate into preimplantation host morula via diploid aggregation, unique to bona fide pluripotent cells. In utero, iPS-derived chimera executed differentiation programs to construct normal heart parenchyma patterning. Within infarcted hearts in the adult, intramyocardial delivery of iPS yielded progeny that properly engrafted without disrupting cytoarchitecture in immunocompetent recipients. In contrast to parental nonreparative fibroblasts, iPS treatment restored postischemic contractile performance, ventricular wall thickness, and electric stability while achieving in situ regeneration of cardiac, smooth muscle, and endothelial tissue. CONCLUSIONS:Fibroblasts reprogrammed by human stemness factors thus acquire the potential to repair acute myocardial infarction, establishing iPS in the treatment of heart disease.

journal_name

Circulation

journal_title

Circulation

authors

Nelson TJ,Martinez-Fernandez A,Yamada S,Perez-Terzic C,Ikeda Y,Terzic A

doi

10.1161/CIRCULATIONAHA.109.865154

subject

Has Abstract

pub_date

2009-08-04 00:00:00

pages

408-16

issue

5

eissn

0009-7322

issn

1524-4539

pii

CIRCULATIONAHA.109.865154

journal_volume

120

pub_type

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