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

Timothy J. Nelson, Almudena Martinez-Fernandez, Satsuki Yamada, Carmen Perez-Terzic, Yasuhiro Ikeda, Andre Terzic

Research output: Contribution to journalArticlepeer-review

368 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)408-416
Number of pages9
JournalCirculation
Volume120
Issue number5
DOIs
StatePublished - Aug 2009

Keywords

  • Pluripotent stem cells
  • Regenerative medicine
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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