Stable benefit of embryonic stem cell therapy in myocardial infarction

TLDR

Conventional myocardial infarction therapies limit disease progression but do not promote repair, whereas embryonic stem cells offer potential for cardiogenesis yet lack definitive evidence of therapeutic benefit. The study administered CGR8 embryonic stem cells, pre‑validated for cardiogenicity, into infarcted rat hearts and monitored left ventricular function serially to assess pathological outcomes. Stem cell treatment produced engrafted cardiomyocytes that improved ventricular function for 12 weeks, preserved architecture, reduced scarring and necrosis, and elicited robust beta‑adrenergic responses without adverse events, demonstrating a stable therapeutic benefit.

Abstract

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 myocardial 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.