Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors
Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors
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DOI：
10.1182/blood.v95.3.952.003k27_952_958
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发表时间：
2000-02-01
期刊：
影响因子：
20.3
通讯作者：
Rafii, S
中科院分区：
文献类型：
--
作者：
Peichev, M;Naiyer, AJ;Rafii, S
新出现的数据表明，循环中的人CD 34（+）细胞亚群具有内皮细胞的表型特征。这些细胞是脱落的成熟内皮细胞还是功能性循环内皮前体细胞（CEP）尚不清楚。使用针对人血管内皮受体-2（VEGFR-2）胞外区的单克隆抗体（MoAb），我们已经表明从胎肝（FL）分离的1.2 +/- 0.3%的CD 34（+）细胞、从动员的外周血分离的2 +/- 0.5%的CD 34（+）细胞和从脐带血分离的1.4 +/- 0.5%的CD 34（+）细胞是VEGFR-2（+）。此外，大多数CD 34（+）VEGFR-2（+）细胞表达造血干细胞标志物AC 133。由于成熟的内皮细胞不表达AC 133，CD 34（+）细胞上VEGFR-2和AC 133的共表达在表型上构成了一个独特的CEP群体。CD 34（+）VEGFR-2（+）细胞表达内皮特异性标志物，包括VE-钙粘蛋白和E-选择素。此外，几乎所有的CD 34（+）VEGFR-2（+）细胞表达趋化因子受体CXCR 4，并响应于基质衍生因子（SDF）-1或VEGF而迁移。为了定量产生内皮集落的CD 34（+）细胞的铺板效率，将来源于FL的CD 34（+）细胞与VEGF和成纤维细胞生长因子（FGF）-2孵育，随后分离并用VEGF和FGF-2接种非贴壁FL衍生的VEGFR-2（+）细胞，导致AC 133（+）VEGFR-2（+）细胞分化为贴壁AC 133（-）VEGFR-2（+）Ac-LDL+细胞。（乙酰化低密度脂蛋白）集落（平板接种效率为3%）。在体内人体模型中，我们发现在左心室辅助装置表面上形成的新生内膜被AC 133（+）VEGFR-2（+）细胞定殖。这些数据表明，表达VEGFR-2和AC 133的循环CD 34（+）细胞构成了一个表型和功能不同的循环内皮细胞群体，可能在新血管生成中发挥作用。(C)2000年，美国血液学会。
Emerging data suggest that a subset of circulating human CD34(+) cells have phenotypic features of endothelial cells. Whether these cells are sloughed mature endothelial cells or functional circulating endothelial precursors (CEPs) is not known. Using monoclonal antibodies (MoAbs) to the extracellular domain of the human Vascular endothelial receptor-2 (VEGFR-2), we have shown that 1.2 +/- 0.3% of CD34(+) cells isolated from fetal liver (FL), 2 +/- 0.5% from mobilized peripheral blood, and 1.4 +/- 0.5% from cord blood were VEGFR-2(+). In addition, most CD34(+)VEGFR-2(+) cells express hematopoietic stem cell marker AC133. Because mature endothelial cells do not express AC133, coexpression of VEGFR-2 and AC133 on CD34(+) cells phenotypically Identifies a unique population of CEPs. CD34(+)VEGFR-2(+) cells express endothelial-specific markers, including VE-cadherin and E-selectin, Also, virtually all CD34(+)VEGFR-2(+) cells express the chemokine receptor CXCR4 and migrate in response to stromal derived factor (SDF)-1 or VEGF, To quantitate the plating efficiency of CD34(+) cells that give rise to endothelial colonies, CD34(+) cells derived from FL were Incubated with VEGF and fibroblast growth factor (FGF)-2, Subsequent isolation and plating of nonadherent FL-derived VEGFR-2(+) cells with VEGF and FGF-2 resulted in differentiation of AC133(+) VEGFR-2(+) cells Into adherent AC133(-)VEGFR-2(+)Ac-LDL+ (acetylated low-density lipoprotein) colonies (plating efficiency of 3%). In an In vivo human model, we have found that the neointima formed on the surface of left ventricular assist devices is colonized with AC133(+)VEGFR-2(+) cells. These data suggest that circulating CD34(+) cells expressing VEGFR-2 and AC133 constitute a phenotypically and functionally distinct population of circulating endothelial cells that may play a role In neo-angiogenesis.(C) 2000 by The American Society of Hematology.