Angiogenesis-like activity of endothelial cells co-cultured with VEGF-producing smooth muscle cells
Angiogenesis-like activity of endothelial cells co-cultured with VEGF-producing smooth muscle cells
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DOI：
10.1089/ten.2006.12.381
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发表时间：
2006-02-01
影响因子：
--
通讯作者：
West, JL
中科院分区：
文献类型：
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作者：
Elbjeirami, WM;West, JL
已经研究了许多策略来改善缺血和生物工程组织的治疗性血管化。在这些研究中，我们基因修饰血管平滑肌细胞（VSMC），以促进内皮细胞增殖，迁移和微血管网络的形成。VSMCs被病毒转导以产生血管内皮生长因子（VEGF），其充当内皮细胞（EC）的化学引诱物和有丝分裂原。用VEGF（165）cDNA转导的VSMC产生显著水平的蛋白质（2 - 4 ng/ 10（5）细胞/天）。转染VEGF的平滑肌细胞或其条件培养液可促进内皮细胞增殖。在两个体外系统中探索了内皮细胞对VEGF产生细胞的趋化反应，即改良的Boyden室试验和2-D栅栏式迁移试验，两者都表明内皮细胞对VEGF转染细胞的迁移反应增加。此外，在VEGF转染的SMC上接种的内皮细胞形成毛细血管样结构。这些结果表明，VSMC基因修饰产生VEGF可能是一种潜在的传递机制，以增强内皮细胞迁移和随后的毛细血管形成，这反过来又可以改善缺血或再生组织的血管化。此外，该系统可以潜在地用作评价新的血管生成和抗血管生成化合物的体外试验床。
A number of strategies have been investigated to improve therapeutic vascularization of ischemic and bioengineered tissues. In these studies, we genetically modified vascular smooth muscle cells (VSMC) to promote endothelial cell proliferation, migration, and formation of microvascular networks. VSMCs were virally transduced to produce vascular endothelial growth factor ( VEGF), which acts as a chemoattractant and mitogen of endothelial cells (EC). VSMCs transduced with VEGF(165) cDNA produced significant levels of the protein ( 2 - 4 ng/ 10(5) cell/day). The proliferation of ECs increased after exposure to VEGF-transfected SMCs or their conditioned media. The chemotactic response of ECs to the VEGF-producing cells was explored in two in vitro systems, the modified Boyden chamber assay and a 2-D fence-style migration assay, and both demonstrated increased migration of ECs in response to VEGF-transfected cells. Furthermore, endothelial cells seeded on top of the VEGF-transfected SMCs formed capillary-like structures. These results suggest that VSMCs genetically modified to produce VEGF could be a potential delivery mechanism to enhance endothelial cell migration and subsequent capillary formation, which in turn could improve vascularization of ischemic or regenerating tissue. Furthermore, this system could potentially be used as an in vitro test bed for evaluation of novel angiogenic and anti-angiogenic compounds.