A novel method to inhibit apoptosis and promote differentiation of induced pluripotent stem cells in transplantation therapy for myocardial infarction

Abstract

Myocardial ischemic disorders are the leading causes of mortality worldwide, and current therapies only delay progression of these diseases. Traditional stem cell therapies face various impediments, including the typical ethical and immunological problems in clinical application. Recently, induced pluripotent stem (iPS) cells have been shown to offer a novel fascinating route to patient-specific and disease-specific pluripotent cells, without the technical and ethical limitations of somatic cell nuclear transfer method. However, iPS cells' limited viability after transplantation in infarcted microenvironment, and low rate of differentiation into cardiovascular tissues restricts their regenerative capacity. Genetically modified iPS cells with the recently discovered cellular repressor of E1A-stimulated genes (CREG), which inhibits apoptosis and inflammation but enhances differentiation, may resolve these crucial problems. Possible mechanisms may include CREG promotion of angiogenesis by VEGF, suppression of inflammation and resistance of apoptosis via activating PI3K/Akt and blocking p38 MARK signaling, and maintenance of endothelial differentiation conditions. The exact mechanisms that CREG can modulate iPS cells' survival and differentiation remain to be investigated.