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人胎主动脉血管祖细胞:鉴定及在缺血性疾病中的潜在应用。

Human fetal aorta-derived vascular progenitor cells: identification and potential application in ischemic diseases.

机构信息

Neurobiology and Neuroregenerative Therapies Unit, Fondazione IRCCS Neurological Institute "Carlo Besta", Milan, Italy.

出版信息

Cytotechnology. 2008 Sep;58(1):43-7. doi: 10.1007/s10616-008-9167-7. Epub 2008 Oct 18.

DOI:10.1007/s10616-008-9167-7
PMID:19002770
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2593754/
Abstract

Vasculogenesis, the formation of blood vessels in embryonic or fetal tissue mediated by immature vascular cells (i.e., angioblasts), is poorly understood. Here we report a summary of our recent studies on the identification of a population of vascular progenitor cells (VPCs) in human fetal aorta. These undifferentiated mesenchymal cells co-express endothelial and myogenic markers (CD133+, CD34+, KDR+, desmin+) and are localized in outer layer of the aortic stroma of 11-12 weeks old human fetuses. Under stimulation with VEGF-A or PDGF-BB, VPCs give origin to a mixed population of mature endothelial and mural cells, respectively. When embedded in a three-dimensional collagen gel, VPCs organize into cohesive cellular cords that resembled mature vascular structures. The therapeutic efficacy of a small number of VPCs transplanted into ischemic limb muscle was demonstrated in immunodeficient mice. Investigation of the effect of VPCs on experimental heart ischemia and on diabetic ischemic ulcers in mice is in progress and seems to confirm their efficacy. On the whole, fetal aorta represents an important source for the investigation of phenotypic and functional features of human vascular progenitor cells.

摘要

血管发生,即在胚胎或胎儿组织中由未成熟的血管细胞(即血管母细胞)介导的血管形成,其机制尚不清楚。在这里,我们报告了我们最近关于鉴定人胎儿主动脉中血管祖细胞(VPC)群体的研究总结。这些未分化的间充质细胞共同表达内皮和肌源性标志物(CD133+、CD34+、KDR+、结蛋白+),并定位于 11-12 周龄人胎儿主动脉基质的外皮层。在 VEGF-A 或 PDGF-BB 的刺激下,VPC 分别起源于成熟的内皮和壁细胞的混合群体。当嵌入三维胶原凝胶中时,VPC 组织成类似成熟血管结构的有凝聚力的细胞索。在免疫缺陷小鼠中,已证明少量 VPC 移植到缺血肢体肌肉中的治疗效果。目前正在研究 VPC 对实验性心肌缺血和糖尿病性缺血性溃疡的影响,似乎证实了它们的疗效。总的来说,胎儿主动脉是研究人类血管祖细胞表型和功能特征的重要来源。

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本文引用的文献

1
Human CD133+ progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis and activation of Wnt signaling.人CD133+祖细胞通过旁分泌刺激血管生成和激活Wnt信号通路促进糖尿病缺血性溃疡的愈合。
Circ Res. 2009 May 8;104(9):1095-102. doi: 10.1161/CIRCRESAHA.108.192138. Epub 2009 Apr 2.
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Human fetal aorta contains vascular progenitor cells capable of inducing vasculogenesis, angiogenesis, and myogenesis in vitro and in a murine model of peripheral ischemia.人类胎儿主动脉含有血管祖细胞,这些细胞能够在体外以及外周缺血的小鼠模型中诱导血管生成、血管新生和肌生成。
Am J Pathol. 2007 Jun;170(6):1879-92. doi: 10.2353/ajpath.2007.060646.
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Discordant developmental waves of angioblasts and hemangioblasts in the early gastrulating mouse embryo.原肠胚形成早期小鼠胚胎中血管母细胞和成血管细胞的不同发育波
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The meso-angioblast: a multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues.中胚层血管母细胞:一种多能、自我更新的细胞,起源于背主动脉,可分化为大多数中胚层组织。
Development. 2002 Jun;129(11):2773-83. doi: 10.1242/dev.129.11.2773.
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Blood. 2001 Nov 1;98(9):2615-25. doi: 10.1182/blood.v98.9.2615.
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Human vasculogenesis ex vivo: embryonal aorta as a tool for isolation of endothelial cell progenitors.人源体外血管生成:以胚胎主动脉作为分离内皮细胞祖细胞的工具。
Lab Invest. 2001 Jun;81(6):875-85. doi: 10.1038/labinvest.3780296.
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Direct isolation of human central nervous system stem cells.人中枢神经系统干细胞的直接分离
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14720-5. doi: 10.1073/pnas.97.26.14720.
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Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors.源自胚胎干细胞的Flk1阳性细胞可作为血管祖细胞。
Nature. 2000 Nov 2;408(6808):92-6. doi: 10.1038/35040568.
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Single-cell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells.静止和激活的小鼠骨骼肌卫星细胞中调控基因表达的单细胞分析
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