Effect of Endothelial Progenitor Cells Transplantation on Neointimal Hyperplasia and Reendothelialization after Balloon Catheter Injury in Rat Carotid Arteries

Abstract

Background: Reendothelialization is a natural pathway to inhibit neointimal hyperplasia and in-stent restenosis. Circulating endothelial progenitor cells (EPCs) derived from bone marrow might contribute to endothelial repair. However, the temporal and spatial distribution of injured vascular reendothelialization and neointimal hyperplasia in the presence of transplanted EPCs is not quite clear. Methods: We performed a carotid balloon injury model and treated by transplantation of bone marrow-derived EPCs. To evaluate the temporal and spatial distribution of neointimal hyperplasia and reendothelialization after injury, the carotid arteries were harvested at different time points after transplantation. Results: Transplanted EPCs labeled by PKH26 were clearly observed attaching on the injured luminal surface at day 1 post-injury. For the undamaged arteries, the transplanted EPCs never adhered to the luminal surface. From day 4 post-injury, the average value of PKH26 fluorescence decreased significantly. Although transplanted EPCs were decreased significantly at the site of injury on day 4 after transplantation, reendothelialization at the site of the injury and inhibition of neointimal hyperplasia were significantly promoted by transplanted EPCs. The degree of reendothelialization of EPC7d (group of EPCs transplantation after balloon injury and harvested at day 7 post-transplantation)/EPC14d was significantly better than that of the BI7d (group of medium injection after balloon injury and harvested at day 7 post-injection)/BI14d, and the statistical difference of neointimal hyperplasia began to appear between EPC14d and BI14d. The number of endothelial cells on the lumen surface of EPC14d increased than that of BI14d, and the number of infiltrated macrophages at the injury site decreased.Conclusions: Transplanted EPCs had chemotactic enrichment and attached to the injured arterial intima after transplantation. Although decreased significantly at the site of injury over time after transplantation, transplanted EPCs could still promote the reendothelialization at the site of the injury and inhibition of neointimal hyperplasia.