contribution of recipient-derived cells in allograft neointima formation and the response to stent implantation的贡献recipient-derived细胞同种异体移植物neointima形成和支架植入术的响应.pdf

Contribution of Recipient-Derived Cells in Allograft Neointima Formation and the Response to Stent Implantation Xiaoli Ma, Benjamin Hibbert, Dawn White, Richard Seymour, Stewart C. Whitman, Edward R. O’Brien* Vascular Biology Laboratory, University of Ottawa Heart Institute, Ottawa, Ontario, Canada Abstract Allograft coronary disease is the dominant cause of increased risk of death after cardiac transplantation. While the percutaneous insertion of stents is the most efficacious revascularization strategy for allograft coronary disease there is a high incidence of stent renarrowing. We developed a novel rabbit model of sex-mismatched allograft vascular disease as well as the response to stent implantation. In situ hybridization for the Y-chromosome was employed to detect male cells in the neointima of stented allograft, and the population of recipient derived neointimal cells was measured by quantitative polymerase chain reaction and characterized by immunohistochemistry. To demonstrate the participation of circulatory derived cells in stent neointima formation we infused ex vivo labeled peripheral blood mononuclear cells into native rabbit carotid arteries immediately after stenting. Fourteen days after stenting the neointima area was 58% greater in the stented vs. non-stented allograft segments (p = 0.02). Male cells were detected in the neointima of stented female-to-male allografts. Recipient-derived cells constituted 72.165.7% and 81.564.2% of neointimal cell population in the non-stented and stented segments, respectively and the corresponding proliferation rates were only 2.760.5% and 2.3 60.2%. Some of the recipient- derived neointimal cells were of endothelial lineage. The ex vivo tagged cells constituted 9.060.4% of the cells per high power field in the stent neointima 14 days after stenting. These experiments provide impo