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皮下基质胶栓的FGF2依赖性新生血管形成由骨髓来源的周细胞和巨噬细胞启动。

FGF2-dependent neovascularization of subcutaneous Matrigel plugs is initiated by bone marrow-derived pericytes and macrophages.

作者信息

Tigges Ulrich, Hyer Elizabeth Gore, Scharf Jeffrey, Stallcup William B

机构信息

Burnham Institute for Medical Research, Cancer Research Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Development. 2008 Feb;135(3):523-32. doi: 10.1242/dev.002071. Epub 2008 Jan 2.

DOI:10.1242/dev.002071
PMID:18171688
Abstract

Vessel-like networks are quickly formed in subcutaneous FGF2-supplemented Matrigel plugs by two cell types: NG2(+) pericytes and F4/80(+) macrophages. Although not detected in these networks until 7 days after plug implantation, the appearance of CD31(+) endothelial cells marks the onset of vessel perfusion and the establishment of mature vessel morphology, with endothelial cells invested tightly by pericytes and more loosely by macrophages. Evidence that mature vessels develop from pericyte/macrophage networks comes from experiments in which 5-day plugs are transplanted into EGFP(+) recipients and allowed to mature. Fewer than 5% of pericytes in mature vessels are EGFP(+) in this paradigm, demonstrating their presence in the networks prior to plug transplantation. Endothelial cells represent the major vascular cell type recruited during later stages of vessel maturation. Bone marrow transplantation using EGFP(+) donors establishes that almost all macrophages and more than half of the pericytes in Matrigel vessels are derived from the bone marrow. By contrast, only 10% of endothelial cells exhibit a bone marrow origin. The vasculogenic, rather than angiogenic, nature of this neovascularization process is unique in that it is initiated by pericyte and macrophage progenitors, with endothelial cell recruitment occurring as a later step in the maturation process.

摘要

在皮下补充了碱性成纤维细胞生长因子2(FGF2)的基质胶栓中,两种细胞类型可快速形成血管样网络:神经胶质抗原2(NG2)阳性周细胞和F4/80阳性巨噬细胞。虽然在栓植入后7天之前在这些网络中未检测到,但CD31阳性内皮细胞的出现标志着血管灌注的开始和成熟血管形态的建立,此时内皮细胞被周细胞紧密包裹,被巨噬细胞包裹得相对松散。成熟血管由周细胞/巨噬细胞网络发育而来的证据来自于将5天的栓移植到增强型绿色荧光蛋白(EGFP)阳性受体中并使其成熟的实验。在此模式下,成熟血管中少于5%的周细胞是EGFP阳性,这表明它们在栓移植之前就已存在于网络中。内皮细胞是血管成熟后期招募的主要血管细胞类型。使用EGFP阳性供体进行骨髓移植证实,基质胶血管中几乎所有的巨噬细胞和一半以上的周细胞都来源于骨髓。相比之下,只有10%的内皮细胞起源于骨髓。这种新生血管形成过程的血管发生性质而非血管生成性质是独特的,因为它由周细胞和巨噬细胞祖细胞启动,内皮细胞的招募是成熟过程中的后期步骤。

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