Stem cell transplant into preimplantation embryo yields myocardial infarction-resistant adult phenotype.
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.
Yamada
Satsuki
S
Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Nelson
Timothy J
TJ
Behfar
Atta
A
Crespo-Diaz
Ruben J
RJ
Fraidenraich
Diego
D
Terzic
Andre
A
D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000502:physiology; D001757:Blastomeres / Q000166:cytology / Q000502:physiology; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000517:prevention & control*; D009765:Obesity; D033581:Stem Cell Transplantation / Q000379:methods*