Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 287, Issue 2, Pages H471-H479Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01247.2003
Keywords
engraftment; xenotransplant; plasticity; cardiac differentiation; remodeling; heart
Funding
- NHLBI NIH HHS [HL-64822, HL-07111, R01 HL064822] Funding Source: Medline
- NIGMS NIH HHS [GM-65841] Funding Source: Medline
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Conventional therapies for myocardial infarction attenuate disease progression without contributing significantly to repair. Because of the capacity for de novo cardiogenesis. embryonic stem cells are considered a potential source for mvocardial regeneration, yet limited information is available on their ultimate therapeutic value. We treated infarcted rat hearts with CGR8 embryonic stem cells preexamined for cardiogenicity, serially probed left ventricular function, and determined final pathological outcome. Stem cell delivery generated new cardiomyocytes of embryonic stem cell origin that integrated with host myocardium within infarct regions. This resulted in a functional benefit within 3 wk that remained sustained over 12 wk of continuous follow-up and included a vigorous inotropic response to beta-adrenergic challenge. Integration of stem cell-derived cardiomyocytes was associated with normalized ventricular architecture, little scar. and a decrease in signs of myocardial necrosis. In contrast, sham-treated infarcted hearts exhibited ventricular cavity dilation and aneurysm formation, poor ventricular function, and a lack of response to beta-adrenergic stimulation. No evidence of graft rejection, ectopy, sudden cardiac death. or tumor formation was observed after therapy. These findings indicate that embryonic stem cells, through differentiation within the host myocardium. can contribute to a stable beneficial outcome on contractile function and ventricular remodeling in the infarcted heart.
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