Burger Patricia E, Coetzee Sandra, McKeehan Wallace L, Kan Mikio, Cook Perry, Fan Yong, Suda Toshio, Hebbel Robert P, Novitzky Nicolas, Muller William A, Wilson E Lynette
Department of Immunology, University of Cape Town, Cape Town, South Africa.
Blood. 2002 Nov 15;100(10):3527-35. doi: 10.1182/blood.V100.10.3527.
Recent experiments show that hematopoietic progenitor cell populations contain endothelial precursor cells. We have isolated a population of CD34(+) cells that expresses fibroblast growth factor receptor-1 (FGFR-1) and that differentiates into endothelial cells in vitro. We find that 4.5% +/- 2.1% of CD34(+) cells isolated from bone marrow, cord blood, and mobilized peripheral blood express FGFR-1 and that viable CD34(+)FGFR(+) cells are small, with little granularity, and express both primitive hematopoietic and endothelial markers on their surface. The primitive hematopoietic markers AC133, c-kit, and Thy-1 are coexpressed by 75%, 85%, and 64% of CD34(+)FGFR(+) cells, respectively. Most of the CD34(+)FGFR(+) cells also express antigens found on endothelial cells, such as CD31, vascular endothelial growth factor receptor-2, and the endothelial-specific cell surface marker, vascular endothelial cadherin (VE-cadherin), whereas 56% to 60% of the cells express Tie, Tek, and the endothelial-specific marker, P1H12. The CD34(+)FGFR(+) population is enriched in cells expressing endothelial-specific antigens compared with the CD34(+) population. Isolated CD34(+)FGFR(+) cells grow slowly in culture, are stimulated by fibroblast growth factor-2 and vascular endothelial growth factor, and give rise to cells that express von Willebrand factor and VE-cadherin and that incorporate acetylated low-density lipoprotein. These experiments show that FGFR-1 is expressed by a subpopulation of CD34(+) cells that give rise to endothelial cells in vitro, indicating that this population contains endothelial stem/progenitor cells.
近期实验表明，造血祖细胞群体中含有内皮前体细胞。我们分离出了一群表达成纤维细胞生长因子受体-1（FGFR-1）且能在体外分化为内皮细胞的CD34(+)细胞。我们发现，从骨髓、脐血和动员的外周血中分离出的CD34(+)细胞中有4.5%±2.1%表达FGFR-1，并且存活的CD34(+)FGFR(+)细胞体积小，颗粒少，其表面同时表达原始造血标志物和内皮标志物。原始造血标志物AC133、c-kit和Thy-1分别在75%、85%和64%的CD34(+)FGFR(+)细胞中共同表达。大多数CD34(+)FGFR(+)细胞还表达在内皮细胞上发现的抗原，如CD31、血管内皮生长因子受体-2以及内皮特异性细胞表面标志物血管内皮钙黏蛋白（VE-钙黏蛋白），而56%至60%的细胞表达Tie、Tek以及内皮特异性标志物P1H12。与CD34(+)群体相比，CD34(+)FGFR(+)群体富含表达内皮特异性抗原的细胞。分离出的CD34(+)FGFR(+)细胞在培养中生长缓慢，受到成纤维细胞生长因子-2和血管内皮生长因子的刺激，并产生表达血管性血友病因子和VE-钙黏蛋白且摄取乙酰化低密度脂蛋白的细胞。这些实验表明，FGFR-1由体外能分化为内皮细胞的CD34(+)细胞亚群表达，这表明该群体含有内皮干/祖细胞。
