Intraislet endothelial cells contribute to revascularization of transplanted pancreatic islets
Intraislet endothelial cells contribute to revascularization of transplanted pancreatic islets
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DOI：
10.2337/diabetes.53.5.1318
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发表时间：
2004-05-01
期刊：
影响因子：
7.7
通讯作者：
Powers, AC
中科院分区：
文献类型：
--
作者：
Brissova, M;Fowler, M;Powers, AC
胰岛移植是治疗1型糖尿病的一种新兴疗法。为了存活和发挥功能，移植的胰岛必须再血管化，因为胰岛分离切断了动脉和静脉连接;目前的范例是胰岛再血管化起源于移植受体。因为分离的胰岛保留胰岛内内皮细胞，我们确定这些内皮细胞是否有助于使用标记的内皮细胞（lacZ敲入F1 k-1/VEGFR 2基因）和使用移植的人胰岛的小鼠模型的血管重建。在肾包膜下移植后3-5周，我们发现胰岛血管重建，移植受体血管确实有助于血管重建过程。使用lacZ标记的内皮细胞模型，我们发现胰岛内内皮细胞不仅在移植后存活，而且成为血管化胰岛移植物的功能部分。将人胰岛移植到免疫缺陷小鼠模型中也观察到胰岛内内皮细胞的类似作用。在小鼠模型中，胰岛移植物内的单个血管由供体或受体内皮细胞组成，或者是供体和受体内皮细胞的嵌合体，表明两种内皮细胞来源都有助于新的血管系统。这些观察结果表明，干预措施，以激活，扩增，或维持胰岛内内皮细胞移植前后可能会促进胰岛血管重建，提高胰岛存活，并改善胰岛移植。
Pancreatic islet transplantation is an emerging therapy for type 1 diabetes. To survive and function, transplanted islets must revascularize because islet isolation severs arterial and venous connections; the current paradigm is that islet revascularization originates from the transplant recipient. Because isolated islets retain intraislet endothelial cells, we determined whether these endothelial cells contribute to the revascularization using a murine model with tagged endothelial cells (lacZ knock-in to F1k-1/VEGFR2 gene) and using transplanted human islets. At 3-5 weeks after transplantation beneath the renal capsule, we found that islets were revascularized and that the transplant recipient vasculature indeed contributed to the revascularization process. Using the lacZ-tagged endothelial cell model, we found that intraislet endothelial cells not only survived after transplantation but became a functional part of revascularized islet graft. A similar contribution of intraislet endothelial cells was also seen with human islets transplanted into an immunodeficient mouse model. In the murine model, individual blood vessels within the islet graft consisted of donor or recipient endothelial cells or were a chimera of donor and recipient endothelial cells, indicating that both sources of endothelial cells contribute to the new vasculature. These observations suggest that interventions to activate, amplify, or sustain intraislet endothelial cells before and after transplantation may facilitate islet revascularization, enhance islet survival, and improve islet transplantation.