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Bioengineering with Endothelial Progenitor Cells Improves the Vascular Engraftment of Transplanted Human Islets

机译:具有内皮祖细胞的生物工程改善了移植的人胰岛的血管植入

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Pancreatic islets isolated for transplantation are disconnected from their vascular supply and need to establish a new functional network posttransplantation. Due to poor revascularization, prevailing hypoxia with correlating increased apoptosis rates in experimental studies can be observed for months posttransplantation. Endothelial progenitor cells (EPCs) are bone marrow-derived cells that promote neovascularization. The present study tested the hypothesis that EPCs, isolated from human umbilical cord blood, could be coated to human islet surfaces and be used to promote islet vascular engraftment. Control or EPC bioengineered human islets were transplanted into the renal subcapsular space of nonobese diabetic/severe combined immunodeficiency mice. Four weeks posttransplantation, graft blood perfusion and oxygen tension were measured using laser Doppler flowmetry and Clark microelectrodes, respectively. Vessel functionality was also assessed by in vivo confocal imaging. The vascular density and the respective contribution of human and recipient endothelium were assessed immunohistochemically by staining for human and mouse CD31. Islet grafts with EPCs had substantially higher blood perfusion and oxygen tension than control transplants. Furthermore, analysis of the vascular network of the grafts revealed that grafts containing EPC bioengineered islets had a superior vascular density compared with control grafts, with functional chimeric blood vessels. We conclude that a simple procedure of surface coating with EPCs provides a possibility to improve the vascular engraftment of transplanted human islets. Established protocols are also easily applicable for intraportal islet transplantation in order to obtain a novel directed cellular therapy at the site of implantation in the liver.
机译:分离用于移植的胰岛与血管供应断开,需要建立一个新的功能网络持续性。由于血运重建差,可以观察到实验研究中的凋亡率增加的普遍存脱次生持续的血糖率为持续的几个月。内皮祖细胞(EPC)是促进新血管形成的骨髓衍生细胞。本研究检测了从人脐血中分离的EPCS,可以涂覆到人胰岛表面上并用于促进胰岛血管植入的假设。对照或EPC生物工程人口胰岛移植到非同源糖尿病/严重联合免疫缺陷小鼠的肾亚面容性空间中。使用激光多普勒流动和克拉克微电极测量接枝血液灌注和氧气张力四周。体内共聚焦成像还评估了血管功能。通过用于人和小鼠CD31染色来评估免疫组织化学的血管密度和人和受体内皮的各自贡献。具有EPC的胰岛移植物显着高于对照移植的血液灌注和氧气张力。此外,移植物的血管网络的分析显示,与对照移植物相比,含有EPC生物工程的移植物具有优异的血管密度,与对照移植物相比,具有功能性嵌合血管。我们得出结论,具有EPCS的表面涂层的简单程序提供了改善移植的人胰岛的血管植入的可能性。建立的方案也很容易适用于内部胰岛移植,以便在肝脏中植入部位的新型指导的细胞疗法。

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