High concentrations of H7 human embryonic stem cells at the point of care for acute myocardial infarction

BACKGROUND: Embryonic stem cell (ESC)-derived cardiomyocytes have become one of the most attractive sources of cellular therapy for minimizing heart tissue damage following myocardial infarction (MI). In this study, we investigated the differentiation of BMS-189453-induced H7 human ESCs (hESCs) and purified ESCs in the treatment of induced acute MI. METHODS: BMS-189453 was used to induce the differentiation of H7 hESCs into myocardial ESCs. We further purified ESCs cells. The expression levels of the myocardial-specific protein cardiac troponin T (cTnT) and the ventricular-specific protein Myosin Light Chain 2 (MLC-2V) were detected by western blot. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was used to detect the expression of iroquois homeobox 4 (IRX4), an important transcription factor related to ventricular muscle development. Ultrasound, radionuclides, and Holter monitoring were used to evaluate the therapeutic effect of ESCs on acute MI induced in pigs. RESULTS: Compared with untreated myocardial tissue, myocardial ESCs and purified ESCs improved the outcome in pigs with MI. Treatment with non-purified ESCs and purified ESCs improved the myocardial perfusion grade and ventricular wall motion score index, increased the viable myocardial ratio (VMR), improved the ejection fraction and left ventricular end-diastolic diameter, and reduced the MI area. Further, compared with non-purified ESCs, purified ESCs resulted in fewer side effects and reduced the incidence of ventricular arrhythmias. CONCLUSIONS: In the pig model of acute MI, treatment with ESCs significantly improved myocardial function, increased myocardial mass, and reduced scar tissue formation. Purified ESCs have a better treatment effect than non-purified ESCs and can reduce the incidence of ventricular arrhythmias. This study has unearthed new prospects for the clinical treatment of MI.