Human model system for angiogenesis and molecular mechanisms on function of growth factors involving in the angiogenesis

我们成功地从人大网膜分离出微血管内皮细胞并进行了体外培养。(1)当用剃刀损伤汇合培养的HOME细胞时，发现这种人网膜微血管（HOME）细胞响应于EGF/TGF-α而最有效地迁移。当EGF/TGF-α存在时，胶原凝胶中的小管形成以及组织型纤溶酶原激活物（t-PA）的表达也有效地增强。(2)用TNF-α处理HOME细胞抑制HOME细胞的细胞迁移和小管形成。TNF-α还可进一步诱导HOME细胞中IL-6、bFGF和胶原酶基因的表达。(3)我们还可以建立一种新的共培养系统，以确定共培养的细胞是否可以诱导胶原凝胶中的内皮细胞的小管形成。在该系统中，人角质形成细胞和食管癌细胞可能通过分泌型TGF-α的旁分泌控制诱导HOME细胞的小管形成。本实验室在体外培养的HOME细胞中，对与血管生成相关的基因进行了分离。

We have isolated microvascular endothelial cells from human omentum and successfully cultured in vitro.(1) This human omentum microvascular (HOME) cells were found to be most effectively migrated in response to EGF/TGF-alpha when confluent cultured HOME cells were wounded with razor. Tubulogenesis in collagen gel as well as expression of tissue-type plasminogen activator (t-PA) was also effectively enhanced when EGF/TGF-alpha was present.(2) Treatment of HOME cells with TNF-alpha inhibited both cell migration and tubulogenesis of HOME cells. Furthermore TNF-alpha could further induce expression of IL-6, bFGF and collagenase genes in HOME cells.(3) We could also establish a new co-culture system to determine whether co-cultured cells could induce tubulogenesis of endothelial cells in collagen gels. In this system, human keratinocytes and esophageal cancer cells could induce tubulogenesis of HOME cells possibly through paracrine control by secretory TGF-alpha. In our laboratory, we are nocoisolating genes involving in angiogenesis of HOME cells in culture system.