The role of vascular actors in two dimensional dialogue of human bone marrow stromal cell and endothelial cell for inducing self-assembled network.
The role of vascular actors in two dimensional dialogue of human bone marrow stromal cell and endothelial cell for inducing self-assembled network.
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DOI：
10.1371/journal.pone.0016767
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发表时间：
2011-02-03
期刊：
影响因子：
3.7
通讯作者：
Amedee J
中科院分区：
文献类型：
--
作者：
Li H;Daculsi R;Grellier M;Bareille R;Bourget C;Remy M;Amedee J
血管生成是血管化组织工程的重要组成部分。在这项研究中，我们发现人骨髓基质细胞（HBMSC）和人脐静脉内皮细胞（HUVEC）的二维共培养能够刺激共培养的HUVEC的迁移并诱导自组装网络的形成。在此过程中，血管内皮生长因子（VEGF 165）的表达上调共培养的HBMSC。同时，VEGF 165受体2（KDR）和尿激酶型纤溶酶原激活物（uPA）在共培养的HUVEC中表达上调。功能研究表明，VEGF 165的中和作用阻断了细胞的迁移和重排，下调了uPA及其受体的表达。阻断血管内皮钙粘蛋白（VE-cad）不影响共培养HUVEC的迁移，但抑制自组装网络的形成。结论：共培养可上调HBMSC中VEGF 165的表达; VEGF 165可激活HUVEC中uPA的表达，从而启动HUVEC的迁移和自组装网络的形成。所有这些结果表明，只有HBMSC和HUVEC的直接接触和它们各自的对话才足以刺激可溶性因子的分泌，并激活对自组装网络形成至关重要的分子，这在组织工程血管化中显示出巨大的应用潜力。
Angiogenesis is very important for vascularized tissue engineering. In this study, we found that a two-dimensional co-culture of human bone marrow stromal cell (HBMSC) and human umbical vein endothelial cell (HUVEC) is able to stimulate the migration of co-cultured HUVEC and induce self-assembled network formation. During this process, expression of vascular endothelial growth factor (VEGF165) was upregulated in co-cultured HBMSC. Meanwhile, VEGF165-receptor2 (KDR) and urokinase-type plasminogen activator (uPA) were upregulated in co-cultured HUVEC. Functional studies show that neutralization of VEGF165 blocked the migration and the rearrangement of the cells and downregulated the expression of uPA and its receptor. Blocking of vascular endothelial-cadherin (VE-cad) did not affect the migration of co-cultured HUVEC but suppressed the self-assembled network formation. In conclusion, co-cultures upregulated the expression of VEGF165 in co-cultured HBMSC; VEGF165 then activated uPA in co-cultured HUVEC, which might be responsible for initiating the migration and the self-assembled network formation with the participation of VE-cad. All of these results indicated that only the direct contact of HBMSC and HUVEC and their respective dialogue are sufficient to stimulate secretion of soluble factors and to activate molecules that are critical for self-assembled network formation which show a great application potential for vascularization in tissue engineering.
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