TY - JOUR
T1 - Repair of acute myocardial infarction with induced pluripotent stem cells induced by human stemness factors
AU - Nelson, Timothy J.
AU - Martinez-Fernandez, Almudena
AU - Yamada, Satsuki
AU - Perez-Terzic, Carmen
AU - Ikeda, Yasuhiro
AU - Terzic, Andre
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
KW - Pluripotent stem cells
KW - Regenerative medicine
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=68249094138&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68249094138&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.109.865154
DO - 10.1161/CIRCULATIONAHA.109.865154
M3 - Article
C2 - 19620500
AN - SCOPUS:68249094138
SN - 0009-7322
VL - 120
SP - 408
EP - 416
JO - Circulation
JF - Circulation
IS - 5
ER -