Local transplantation of human thrombomodulin gene-modified endothelial progenitor cells to prevent restenosis after angioplasty

Abstract

Objective To investigate whether restenosis can be inhibited by human thrombomodulin (hTM) gene-modified endothelial progenitor cells (EPCs) after angioplasty. Methods EPCs derived from rabbit periphery blood were modified with hTM gene using lentiviral vector and were incubated with Fe2O3-arginine. Thirty-six New Zealand rabbits were randomly divided into 3 groups. Angioplastywas underwent by Fogarty ballooncatheter via catheterization of right common carotid artery, and then hTM-EPCs, EPCs or equal volume of normal saline were transplanted to the injury sites with blood flow blocked respectively. Histology and Western blotting were performed on 1th week for 4 rabbits from each group to evaluate cell adherence. Magnetic resonance (MR) was performed on 4th and 8th week after transplantation to evaluate restenosis. All of the rest rabbits were sacrificed at the end of 8th week after injury and the injured vessels were harvested for hematoxylin and eosin (HE), elastic tissue and proliferating cell nuclear antigen (PCNA) staining to observe the vascular wall structure and degree of intimal hyperplasia and smooth muscle proliferation. Results Prussian blue staining showed iron-labeled cells distributed in the injured artery intima. Western blotting indicated that injured vascular transplanted with hTM-EPCs overexpressed thrombomodulin than other two groups. MR showed that the stenotic degree of the lumen in hTM-EPCs group was less serious than other two groups. The histopathological study on 8th week showed that the neointimal/media ratio (N/M) in hTM-EPCs group, EPCs group and control group was 0.348±0.040, 0.704±0.060 and 1.294±0.051, respectively (P=0.000); the ratio of restenosis in each group was (11.4±2.3)%, (24.3±4.8)% and (35.2±9.4)%, respectively (P=0.005); and the PCNA positive cell index in each group was (12.3±3.9)%, (23.4±4.2)% and (49.3±6.8)%, respectively (P=0.000). Conclusion The local transplantation of hTM-EPCs can prevent restenosis through Fogarty balloon after angioplasty in rabbit model. Key words: Thrombomodulin; Endothelial progenitor cells; Balloon injury; Restenosis