Mesenchymal stem cells overexpressing GCP-2 improve heart function through enhanced angiogenic properties in a myocardial infarction model

Abstract

In this study, our aim was to evaluate the angio-vasculogenic properties of human adipose tissue-derived mesenchymal stem cells overexpressing GCP-2 (hASCs/GCP-2) and to determine their therapeutic effects on an experimental ischemic heart model. Quantitative real-time (qRT)-PCR results revealed that hASCs/GCP-2 expressed significantly higher levels of pro-angiogenic genes including vascular endothelial growth factor (VEGF)-A, hepatocyte growth factor (HGF), and interleukin (IL)-8 when compared to control-vector transduced hASCs or HUVECs. In addition, the anti-apoptotic insulin-like growth factor (IGF)-1 and Akt-1 were also highly up-regulated in the hASCs/GCP-2 cells. In vitro cell migration and proliferation assays showed that hASCs/GCP-2-derived conditioned media (CM) significantly accelerated migration and proliferation of fibroblast cells. Examination of in vitro endothelial differentiation showed that hASCs/GCP-2 cells spontaneously formed vascular-like structures and highly expressed endothelium-specific genes and proteins. In vivo study results of our mice myocardial infarction (MI) model revealed that hASCs/GCP-2 implantation improved cardiac function and reduced infarct size. Finally, transplanted hASCs/GCP-2 cells differentiated unexpectedly into endothelial cells and the engraftment rate was significantly higher than control groups. We suggest that overexpression of GCP-2 in stem cells has the potential to enhance their angiogenic and survival properties.