Stem cell transplant into preimplantation embryo yields myocardial infarction-resistant adult phenotype

Satsuki Yamada, Timothy J. Nelson, Atta Behfar, Ruben J. Crespo-Diaz, Diego Fraidenraich, Andre Terzic

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Stem cells are an emerging strategy for treatment of myocardial infarction, limited however to postinjury intervention. Preventive stem cell-based therapy to augment stress tolerance has yet to be considered for lifelong protection. Here, pluripotent stem cells were microsurgically introduced at the blastocyst stage of murine embryo development to ensure stochastic integration and sustained organ contribution. Engineered chimera displayed excess in body weight due to increased fat deposits, but were otherwise devoid of obesity-related morbidity. Remarkably, and in sharp contrast to susceptible nonchimeric offspring, chimera was resistant to myocardial infarction induced by permanent coronary occlusion. Infarcted nonchimeric adult hearts demonstrated progressive deterioration in ejection fraction, while age-matched 12-14-months-old chimera recovered from equivalent ischemic insult to regain within one-month preocclusion contractile performance. Electrical remodeling and ventricular enlargement with fibrosis, prominent in failing nonchimera, were averted in the chimeric cohort characterized by an increased stem cell load in adipose tissue and upregulated markers of biogenesis Ki67, c-Kit, and stem cell antigen-1 in the myocardium. Favorable outcome in infarcted chimera translated into an overall benefit in workload capacity and survival. Thus, prenatal stem cell transplant yields a cardioprotective phenotype in adulthood, expanding cell-based indications beyond traditional postinjury applications to include pre-emptive therapy.

Original languageEnglish (US)
Pages (from-to)1697-1705
Number of pages9
JournalStem Cells
Volume27
Issue number7
DOIs
StatePublished - Jul 2009

Keywords

  • Blastocyst
  • Chimera
  • Embryonic stem cells
  • Heart disease
  • Prenatal therapy
  • Prevention

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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