Contribution of Recipient-Derived Cells in Allograft Neointima Formation and the Response to Stent Implantation
Contribution of Recipient-Derived Cells in Allograft Neointima Formation and the Response to Stent Implantation
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DOI：
10.1371/journal.pone.0001894
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发表时间：
2008-03-26
期刊：
影响因子：
3.7
通讯作者：
O'Brien, Edward R.
中科院分区：
文献类型：
--
作者：
Ma, Xiaoli;Hibbert, Benjamin;O'Brien, Edward R.
同种异体冠状动脉疾病是心脏移植后死亡风险增加的主要原因。尽管经皮支架置入术是同种移植物冠状动脉疾病最有效的血运重建策略，但支架重排的发生率很高。我们开发了一种新的兔性错配同种异体血管疾病模型，以及支架植入后的反应。用Y染色体原位杂交法检测移植血管新生内膜中的雄性细胞，用定量聚合酶链式反应检测受体来源的新生内膜细胞的数量，并用免疫组织化学方法进行鉴定。为了证实循环衍生细胞参与支架新生内膜的形成，我们在支架置入后立即将体外标记的外周血单个核细胞注入天然兔颈动脉。支架植入14天后，有支架的同种异体移植段的新生内膜面积比无支架的移植段大58%(p=0.02)。带支架的雌雄同种异体移植物的新生内膜中可检测到雄性细胞。受体来源的细胞分别占非支架段和支架段新生内膜细胞总数的72.1+/-5.7%和81.5+/-4.2%，相应的增殖率仅为2.7+/-0.5%和2.3+/-0.2%。部分受体来源的新生内膜细胞为内皮细胞系。支架置入后14天，支架内每高倍视野内标记细胞占9.0+/-0.4%。这些实验提供了重要的定量数据，说明宿主来源的血源性细胞在多大程度上促进了移植物血管病变新生内膜的形成，以及支架植入的早期反应。
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 72.1 +/- 5.7% and 81.5 +/- 4.2% of neointimal cell population in the non-stented and stented segments, respectively and the corresponding proliferation rates were only 2.7 +/- 0.5% and 2.3 +/- 0.2%. Some of the recipient-derived neointimal cells were of endothelial lineage. The ex vivo tagged cells constituted 9.0 +/- 0.4% of the cells per high power field in the stent neointima 14 days after stenting. These experiments provide important quantitative data regarding the degree to which host-derived blood-borne cells contribute to neointima formation in allograft vasculopathy and the early response to stent implantation.