Abstract
Induced pluripotent stem (iPS) cells have the potential to differentiate to various types of cardiovascular cells to repair an injured heart. The potential therapeutic benefits of iPS cell based treatment have been established in small-animal models of myocardial infarction (MI). We hypothesize that porcine iPS (piPS) cell transplantation may be an effective treatment for MI. After a 90-minute occlusion of the left anterior descending artery in a porcine model, undifferentiated piPS cells or PBS were injected into the ischemic myocardium. Cardiac function, myocardial perfusion and cell differentiation were investigated. One week after piPS cell delivery, global left ventricular ejection fraction (LVEF) significantly decreased in both the iPS group and the PBS group compared to the Sham group (p<0.05, respectively). Six weeks after piPS cell delivery, LVEF of the iPS group significantly improved compared to the PBS group (56.68% vs. 50.93%, p = 0.04) but was still lower than the Sham group. Likewise, the piPS cell transplantation improved the regional perfusion compared to the PBS injection (19.67% vs. 13.67%, p = 0.02). The infarct area was significantly smaller in the iPS group than the PBS group (12.04% vs. 15.98% p = 0.01). PiPS cells engrafted into the myocardium can differentiate into vessel cells, which result in increased formation of new vessels in the infarcted heart. Direct intramyocardial injection of piPS cells can decrease infarct size and improve left ventricular function and perfusion for an immunosuppressed porcine AMI model.
Highlights
Novel embryonic stem cell (ESC)-like pluripotent stem cells, induced pluripotent stem cells, were first generated from murines by transducing adult dermal fibroblasts with retroviruses encoding Oct3/4, Sox2, c-Myc, and Klf4 [1]
Left ventricular end-diastolic pressure (LVEDP) was significantly higher in the PBS group at the 7th week, but there was no difference in other hemodynamic parameters, such as left ventricular end-diastolic pressure (LVSP), aortic systolic pressure (Ao-SP) and aortic diastolic pressure (Ao-DP), among the three groups
This result indicates that elevated LVEDP induced by myocardial infarction (MI) can be attenuated by porcine iPS (piPS) cells treatment
Summary
Novel embryonic stem cell (ESC)-like pluripotent stem cells, induced pluripotent stem (iPS) cells, were first generated from murines by transducing adult dermal fibroblasts with retroviruses encoding Oct3/4, Sox, c-Myc, and Klf4 [1]. IPS cells are capable of differentiating into various types of cells as needed, including cardiovascular cells [6,7]. Compared to MSCs and ESCs, iPS cells are more accessible, and offer the possibility of generating patient-specific cell types for use in regenerative medicine. IPS cells may have fewer ethical issues and eliminate the problem of immune rejection [9]. It may represent the most promising candidate for personalized medicine. The generation of iPS cells offers the option of autologous transplantation, and provides a new tool for cellular therapy for ischemic heart disease
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