Open AccessStem Cell Transplant into Preimplantation Embryo Yields Myocardial Infarction‐Resistant Adult Phenotype
Author(s) -
Yamada Satsuki,
Nelson Timothy J.,
Behfar Atta,
CrespoDiaz Ruben J.,
Fraidenraich Diego,
Terzic Andre
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.116
Subject(s) - stem cell , biology , chimera (genetics) , induced pluripotent stem cell , ventricular remodeling , stem cell therapy , myocardial infarction , medicine , cardiology , embryonic stem cell , immunology , microbiology and biotechnology , genetics , gene
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. STEM CELLS 2009;27:1697–1705