Department of Vascular Surgery, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1844-51. doi: 10.1161/ATVBAHA.113.300902. Epub 2013 Jun 6.
This 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.
A 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 ≈ 30% of neointimal SMCs.
We 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.
本研究旨在对血管外膜中的干细胞进行特征描述，并阐明其在静脉移植物动脉粥样硬化发病机制中的功能作用。
使用小鼠静脉移植物模型来研究外膜干细胞/前体细胞在动脉粥样硬化中的功能作用。静脉移植物的外膜在血管移植的早期阶段经历了显著的重塑，并表现出明显的异质细胞组成。免疫荧光染色表明存在大量与血管周围组织（vasa vasorum）密切相关的干细胞抗原-1阳性细胞。体外集落形成实验表明，外膜细胞培养物的生长率为 1%至 11%，其中大多数可分化为平滑肌细胞（SMCs）。这些干细胞抗原-1阳性细胞还显示出在体外分化为成脂细胞、成骨细胞或软骨细胞谱系的潜能。鉴于 SMCs 在动脉粥样硬化中的促动脉粥样硬化作用，我们专注于前体细胞-SMC 分化的功能作用，随后证明其由整合素/胶原 IV 轴的直接相互作用驱动。体外生物反应器系统揭示了干细胞抗原-1阳性前体细胞在基质细胞衍生因子-1作用下向血管壁迁移的能力。移植到静脉移植物外层的干细胞抗原-1阳性细胞在载脂蛋白 E 缺陷小鼠中表现出增强的动脉粥样硬化，约占新生内膜 SMC 的 30%。
我们证明，在静脉移植的病理条件下，外膜中存在能够通过分化为 SMC 而积极参与血管疾病发病机制的干细胞/前体细胞。
