Repair of Acute Myocardial Infarction by Human Stemness Factors Induced Pluripotent Stem Cells

TLDR

Nuclear reprogramming enables generation of embryo‑independent pluripotent stem cells from somatic tissue, and induced pluripotent stem cells (iPS) show promise for cardiac differentiation, though their therapeutic potential for heart disease had not yet been evaluated. The study aimed to determine whether fibroblasts transduced with OCT3/4, SOX2, KLF4, and c‑MYC could generate iPS cells capable of repairing acute myocardial infarction. The authors produced iPS cells from fibroblasts, delivered them intramyocardially into infarcted hearts, and observed engraftment and differentiation into cardiac, smooth muscle, and endothelial cells without disrupting tissue.

Abstract

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.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.Fibroblasts reprogrammed by human stemness factors thus acquire the potential to repair acute myocardial infarction, establishing iPS in the treatment of heart disease.