Role of vascular endothelial growth factor in bone marrow stromal cell modulation of endothelial cells

Role of vascular endothelial growth factor in bone marrow stromal cell modulation of endothelial cells
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DOI:
10.1089/107632703762687573
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发表时间:
2003-02-01
期刊:
影响因子:
--
通讯作者:
Mooney, DJ
Mooney, DJ
中科院分区:
生物2区
文献类型:
--
作者:
Kaigler, D;Krebsbach, PH;Mooney, DJ

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使用细胞移植的组织工程策略的基本原则之一是新形成的组织必须获得并保持足够的血管化以支持其生长。通过递送生长因子来增强血管生成是建立这些组织的血管网络的一种方法。在这项研究中,我们测试了骨髓基质细胞(BMSCs)的潜力,调节血管前体细胞,内皮细胞(ECs)的生长和分化活动,通过分泌可溶性血管生成因子。BMSC条件培养液(CM)可促进培养的内皮细胞的生长和分化。酶联免疫吸附试验表明,小鼠和人BMSC分泌大量的血管内皮生长因子(VEGF)(2.4-3.1 ng/10(6)个细胞/天)。此外,用阻断抗体消除BMSC分泌的VEGF的活性完全阻断CM对培养的EC的作用。这些数据表明,人BMSC分泌足够量的VEGF,以提高体外内皮细胞的存活和分化,并表明它们可能能够直接协调体内血管生成。
One of the fundamental principles that underlies tissue-engineering strategies using cell transplantation is that a newly formed tissue must acquire and maintain sufficient vascularization in order to support its growth. Enhancing angiogenesis through delivery of growth factors is one approach to establishing a vascular network to these tissues. In this study, we tested the potential of bone marrow stromal cells (BMSCs) to modulate the growth and differentiation activities of blood vessel precursors, endothelial cells (ECs), by their secretion of soluble angiogenic factors. The growth and differentiation of cultured ECs were enhanced in response to exposure to BMSC conditioned medium (CM). Enzyme-linked immunosorbent assays demonstrated that both mouse and human BMSCs secreted significant quantities of vascular endothelial growth factor (VEGF) (2.4-3.1 ng/10(6) cells per day). Furthermore, eliminating the activity of BMSC-secreted VEGF with blocking antibodies completely blocked the CM effects on cultured ECs. These data demonstrate that human BMSCs secrete sufficient quantities of VEGF to enhance survival and differentiation of endothelial cells in vitro, and suggest they may be capable of directly orchestrating angiogenesis in vivo.