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一群多能性CD34阳性脂肪基质细胞具有周细胞和间充质表面标志物,位于内皮细胞周围,并稳定内皮网络。

A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks.

作者信息

Traktuev Dmitry O, Merfeld-Clauss Stephanie, Li Jingling, Kolonin Mikhail, Arap Wadih, Pasqualini Renata, Johnstone Brian H, March Keith L

机构信息

Indiana Center for Vascular Biology & Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

出版信息

Circ Res. 2008 Jan 4;102(1):77-85. doi: 10.1161/CIRCRESAHA.107.159475. Epub 2007 Oct 25.

Abstract

It has been shown that stromal-vascular fraction isolated from adipose tissues contains an abundance of CD34+ cells. Histological analysis of adipose tissue revealed that CD34+ cells are widely distributed among adipocytes and are predominantly associated with vascular structures. The majority of CD34+ cells from freshly isolated stromal-vascular fraction were CD31-/CD144- and could be separated from a distinct population of CD34+/CD31+/CD144+ (endothelial) cells by differential attachment on uncoated plastic. The localization of CD34+ cells within adipose tissue suggested that the nonendothelial population of these cells occupied a pericytic position. Analysis of surface and intracellular markers of the freshly isolated CD34+/CD31-/CD144- adipose-derived stromal cells (ASCs) showed that >90% coexpress mesenchymal (CD10, CD13, and CD90), pericytic (chondroitin sulfate proteoglycan, CD140a, and CD140b), and smooth muscle (alpha-actin, caldesmon, and calponin) markers. ASCs demonstrated polygonal self-assembly on Matrigel, as did human microvascular endothelial cells. Coculture of ASCs with human microvascular endothelial cells on Matrigel led to cooperative network assembly, with enhanced stability of endothelial networks and preferential localization of ASCs on the abluminal side of cords. Bidirectional paracrine interaction between these cells was supported by identification of angiogenic factors (vascular endothelial growth factor, hepatocyte growth factor, basic fibroblast growth factor), inflammatory factors (interleukin-6 and -8 and monocyte chemoattractant protein-1 and -2), and mobilization factors (macrophage colony-stimulating factor and granulocyte/macrophage colony-stimulating factor) in media conditioned by CD34+ ASCs, as well a robust mitogenic response of ASCs to basic fibroblast growth factor, epidermal growth factor, and platelet-derived growth factor-BB, factors produced by endothelial cells. These results demonstrate for the first time that the majority of adipose-derived adherent CD34+ cells are resident pericytes that play a role in vascular stabilization by mutual structural and functional interaction with endothelial cells.

摘要

研究表明,从脂肪组织中分离出的基质血管成分含有大量CD34+细胞。脂肪组织的组织学分析显示,CD34+细胞广泛分布于脂肪细胞之间,且主要与血管结构相关。新鲜分离的基质血管成分中的大多数CD34+细胞为CD31-/CD144-,通过在未包被的塑料培养皿上进行差异贴壁,可将其与不同的CD34+/CD31+/CD144+(内皮)细胞群体分离。脂肪组织中CD34+细胞的定位表明,这些细胞的非内皮群体占据了周细胞的位置。对新鲜分离的CD34+/CD31-/CD144-脂肪来源的基质细胞(ASC)的表面和细胞内标志物分析显示,>90%的细胞共表达间充质(CD10、CD13和CD90)、周细胞(硫酸软骨素蛋白聚糖、CD140a和CD140b)和平滑肌(α-肌动蛋白、钙调蛋白和钙泊宁)标志物。ASC在基质胶上呈多边形自我组装,人微血管内皮细胞也是如此。在基质胶上,ASC与人微血管内皮细胞共培养导致协同网络组装,内皮网络稳定性增强,ASC优先定位在索的无腔侧。通过鉴定CD34+ ASC条件培养基中的血管生成因子(血管内皮生长因子、肝细胞生长因子、碱性成纤维细胞生长因子)、炎症因子(白细胞介素-6和-8以及单核细胞趋化蛋白-1和-2)和动员因子(巨噬细胞集落刺激因子和粒细胞/巨噬细胞集落刺激因子),以及ASC对碱性成纤维细胞生长因子、表皮生长因子和血小板衍生生长因子-BB(内皮细胞产生的因子)的强烈促有丝分裂反应,支持了这些细胞之间的双向旁分泌相互作用。这些结果首次证明,大多数脂肪来源的贴壁CD34+细胞是驻留周细胞,它们通过与内皮细胞的相互结构和功能相互作用在血管稳定中发挥作用。

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