Long-term improvement of cardiac function in rats after infarction by transplantation of embryonic stem cells.

Objective: This study was designed to investigate the feasibility of and potential functional improvement with embryonic stem cell transplantation in rats 32 weeks after myocardial infarction.

Methods: Before cell transplantation, cultured embryonic stem cells were transfected with the complementary DNA of green fluorescent protein to identify engrafted cells in myocardium. Myocardial infarction was induced by ligation of the left coronary artery. Either 3 x 10(5) mouse embryonic stem cells or an equivalent volume of cell-free medium was injected into injured myocardium within 20 minutes after induction of myocardial infarction.

Results: Embryonic stem cell transplantation significantly increased the survival rate in rats undergoing myocardial infarction during the experimental period of 32 weeks. Hemodynamic and echocardiographic data showed that embryonic stem cell transplantation significantly improved ventricular function relative to the myocardial infarction plus medium control group. Tissue positive for green fluorescent protein was found in the injured myocardium with cell transplantation. The proportion of myocardium positively immunostained by antibodies against alpha-myosin heavy chain and cardiac troponin I was greater in the infarcted area with embryonic stem cell transplantation than in the injured myocardium with medium injection. Single green fluorescent protein-positive cells with a rod shape and clear striations were observed in cardiomyocytes isolated from infarcted hearts with embryonic stem cell transplantation. In addition, the number of blood vessels in injured myocardium was greater in the cell-transplanted myocardial infarction group than in the medium-injected myocardial infarction group.

Conclusions: Engrafted embryonic stem cells differentiated into cardiomyocytes in injured myocardium, caused an angiogenetic effect, and subsequently improved cardiac function during the 32-week observation period.