Transplantation of human thrombomodulin gene-modified endothelial progenitor cells to prevent vascular restenosis after balloon injury

Abstract

Objective To explore the feasibility of transplantation of human thrombomodulin (hTM) gene-modified endothelial progenitor cells (EPCs) to rabbit carotid artery balloon injury model locally to prevent vascular restenosis.Methods Rabbit peripheral blood mononuclear cells were isolated and EPCs were modified with hTM gene using X-tremeGENE HP DNA Transfection Reagent.Genetically modified EPCs were incubated with Fe2O3-arginine.Sixteen adult New Zealand white rabbits were divided into two groups.hTM gene-modified EPCs,nom-gene modified EPCs and equal volume of normal saline were transplanted to the balloon injury local via Fogarty balloon catheter,respectively.Serial nuclear magnetic resonance (MRI) was performed on 1st,3rd,7th and 14th day after transplantation to assess the loss of MRI signal intensity at the injured sites.Four months later,the carotid arteries were isolated and cut for hematoxylin and eosin (HE) staining and elastic tissue staining to evaluate restenosis.Results The hTM gene could be successfully transfected into EPCs using Transfection Reagent and the efficiency rate was about 10％-15％.EPCs could be partly adhered to the injured site locally via Fogarty balloon catheter and result in the loss of magnetic resonance (MR) signal intensity at the injured sites.The neointimal/media ratio (N/M) in gene modified group,non-gene modified group and injured group was 0.30 ± 0.02,0.62 ± 0.05 and 1.58 ± 0.10,respectively (P ＜ 0.01).Conclusion hTM gene-modified EPCs could effectively prevent vascular restenosis after balloon injury. Key words: Thrombomodulin; Endothelial progenitor cells; Balloon injury; Restenosis