Adventitial Stem Cells in Vein Grafts Display Multilineage Potential That Contributes to Neointimal Formation
Adventitial Stem Cells in Vein Grafts Display Multilineage Potential That Contributes to Neointimal Formation
复制标题
静脉移植物中的外膜干细胞显示出有助于新内膜形成的多谱系潜力
DOI：
10.1161/atvbaha.113.300902
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发表时间：
2013-08-01
影响因子：
8.7
通讯作者：
Xu, Qingbo
中科院分区：
文献类型：
--
作者：
Chen, Yikuan;Wong, Mei Mei;Xu, Qingbo
本研究的目的是进行外膜内的干细胞的特性，并阐明其功能的作用，在静脉移植物atherosclerosis.Approach和ResultsA小鼠静脉移植物模型的发病机制，探讨动脉粥样硬化的外膜干/祖细胞的功能作用。静脉移植物的外膜在血管移植的早期阶段经历了显着的重塑，并显示出显着的异质性细胞组成。免疫荧光染色显示大量的干细胞抗原-1阳性细胞靠近血管。体外克隆形成实验表明，外膜细胞培养物的生长率为1%至11%，其中大部分可以分化为平滑肌细胞（SMCs）。这些干细胞抗原-1-阳性细胞也显示出在体外分化成脂肪、成骨或成软骨谱系的潜力。鉴于SMC在动脉粥样硬化中的致动脉粥样硬化作用，我们重点研究了祖细胞SMC分化的功能作用，随后我们证明了它是由整合素/IV型胶原轴的直接相互作用驱动的。离体生物反应器系统揭示了干细胞抗原-1阳性祖细胞响应基质细胞衍生因子-1进入血管壁的迁移能力。干细胞抗原-1-阳性细胞被应用到静脉移植物的外层表现出增强的动脉粥样硬化载脂蛋白E缺陷小鼠，这有助于约30%的新生内膜SMCs.ConclusionsWe表明，在静脉移植病理条件下，外膜窝藏干/祖细胞，可以积极参与血管疾病的发病机制，通过分化成SMC。
ObjectiveThis study was designed to carry out the characterization of stem cells within the adventitia and to elucidate their functional role in the pathogenesis of vein graft atherosclerosis.Approach and ResultsA mouse vein graft model was used to investigate the functional role of adventitial stem/progenitor cells on atherosclerosis. The adventitia of vein grafts underwent significant remodeling during early stages of vessel grafting and displayed markedly heterogeneous cell compositions. Immunofluorescence staining indicated a significant number of stem cell antigen-1-positive cells that were closely located to vasa vasorum. In vitro clonogenic assays demonstrated 1% to 11% of growing rates from adventitial cell cultures, most of which could be differentiated into smooth muscle cells (SMCs). These stem cell antigen-1-positive cells also displayed a potential to differentiate into adipogenic, osteogenic, or chondrogenic lineages in vitro. In light of the proatherogenic roles of SMCs in atherosclerosis, we focused on the functional roles of progenitor-SMC differentiation, in which we subsequently demonstrated that it was driven by direct interaction of the integrin/collagen IV axis. The ex vivo bioreactor system revealed the migratory capacity of stem cell antigen-1-positive progenitor cells into the vessel wall in response to stromal cell-derived factor-1. Stem cell antigen-1-positive cells that were applied to the outer layer of vein grafts showed enhanced atherosclerosis in apolipoprotein E-deficient mice, which contributed to approximate to 30% of neointimal SMCs.ConclusionsWe demonstrate that during pathological conditions in vein grafting, the adventitia harbors stem/progenitor cells that can actively participate in the pathogenesis of vascular disease via differentiation into SMCs.