Angiostatic factors normally restrict islet endothelial cell proliferation and migration: implications for islet transplantation
Angiostatic factors normally restrict islet endothelial cell proliferation and migration: implications for islet transplantation
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DOI：
10.1111/j.1432-2277.2009.00939.x
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发表时间：
2009-12-01
影响因子：
3.1
通讯作者：
Carlsson, Per-Ola
中科院分区：
文献类型：
--
作者：
Johansson, Asa;Olerud, Johan;Carlsson, Per-Ola
移植后7-14天内，通过供体胰岛内皮细胞的扩张和植入器官的血管向内生长，移植胰岛中新血管形成。然而，一些研究表明，虽然胰岛吸引受体血管，但形成的胰岛内血管网络不足，影响胰岛移植后功能。本研究旨在建立一种体外模型来研究离体肝脏和胰岛内皮细胞的迁移和增殖特性。使用Bandeiraea simplicifolia（BS-1）包被的Dynabeads纯化大鼠胰岛或肝内皮。肝内皮细胞向胰岛条件培养液迁移和增殖增加。通过加入中和血管内皮生长因子（VEGF）抗体，可完全防止这些作用。相反，胰岛产生的VEGF不能诱导胰岛内皮细胞迁移，对胰岛内皮细胞增殖只有轻微的影响。然而，这些特性可以通过阻断内皮抑制素、血小板反应蛋白-1或α（1）-抗胰蛋白酶的作用来激活。总之，VEGF可以吸引受体血管向肝内移植的胰岛，但胰岛内血管扩张受到胰岛和胰岛内皮内存在的血管生成抑制因子的阻碍。移植后早期抑制血管生成抑制因子可能为恢复胰岛血管网络和改善胰岛移植物功能提供一种策略。
P>New blood vessel formation in transplanted islets occurs within 7-14 days post-transplantation through both the expansion of donor islet endothelium and ingrowth of blood vessels from the implantation organ. However, several studies indicate that although the islets attract recipient blood vessels, the formed intra-islet vascular network is insufficient, which affects islet post-transplant function. This study aimed to develop an in vitro model to investigate the migration and proliferation properties of isolated liver and islet endothelium. Rat islet or liver endothelium was purified using Bandeiraea simplicifolia (BS-1)-coated Dynabeads. The liver endothelium displayed an increased migration and proliferation to islet-conditioned medium. These effects were fully prevented by adding a neutralizing vascular endothelial growth factor (VEGF)-antibody. In contrast, islet-produced VEGF failed to induce islet endothelial cell migration and only had marginal effects on islet endothelial cell proliferation. These properties could, however, be activated through blocking the effects of either endostatin, thrombospondin-1 or alpha(1)-antitrypsin. In conclusion, VEGF may attract recipient blood vessels towards intrahepatically transplanted islets, but intra-islet vascular expansion is hampered by angiostatic factors present within the islets and the islet endothelium. Inhibition of angiostatic factors early after transplantation may provide a strategy to restore the islet vascular network and improve islet graft function.