Overexpression of protein kinase C ɛ improves retention and survival of transplanted mesenchymal stem cells in rat acute myocardial infarction

We assessed the effects of protein kinase C ɛ (PKC ɛ ) for improving stem cell therapy for acute myocardial infarction (AMI). Primary mesenchymal stem cells (MSCs) were harvested from rat bone marrow. PKC ɛ -overexpressed MSCs and control MSCs were transplanted into infarct border zones in a rat AMI model. MSCs and PKC ɛ distribution and expression of principal proteins involved in PKC ɛ signaling through the stromal cell-derived factor 1 (SDF-1)/CXC chemokine receptor type 4 (CXCR4) axis and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway were analyzed by immunofluorescence and western blot 1 day after transplantation. Echocardiographic measurements and histologic studies were performed at 4 weeks after transplantation, and MSC survival, expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β (TGF β ), cardiac troponin I (cTnI), von Willebrand factor (vWF), smooth muscle actin (SMA) and factor VIII and apoptosis in infarct border zones were assessed. Rat heart muscles retained more MSCs and SDF-1, CXCR4, PI3K and phosphorylated AKT increased with PKC ɛ overexpression 1 day after transplantation. MSC survival and VEGF, bFGF, TGF β , cTnI, vWF, SMA and factor VIII expression increased in animals with PKC ɛ -overexpressed MSCs at 4 weeks after transplantation and cardiac dysfunction and remodeling improved. Infarct size and apoptosis decreased as well. Inhibitory actions of CXCR4 or PI3K partly attenuated the effects of PKC ɛ . Activation of PKC ɛ may improve retention, survival and differentiation of transplanted MSCs in myocardia. Augmentation of PKC ɛ expression may enhance the therapeutic effects of stem cell therapy for AMI.