In vivo Dynamic Imaging of Angiogenesis in Transplanted Islets

移植胰岛血管生成的体内动态成像

• 批准号: 7224491
• 负责人: EBA H HATHOUT
• 金额: $ 20.13万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224491
• 关键词: angiogenesis; apoptosis; athymic mouse; bioimaging /biomedical imaging; contrast media; hemodynamics; histology; hyperbaric oxygen therapy; hypoxia; hypoxia inducible factor 1; immunocytochemistry; insulin dependent diabetes mellitus; magnetic resonance imaging; method development; nerve growth factors; pancreas imaging /visualization; pancreatic islet transplantation; western blottings

DESCRIPTION (provided by applicant): In vivo imaging of pancreatic islets can provide invaluable information about the life cycle of endogenous and/or transplanted beta-cells in type 1 diabetes. Current in vivo imaging attempts have focused on quantification of islet mass, secretory products, or inflammatory markers. In contrast to microscopy, magnetic resonance imaging (MRI) can non-invasively deliver high resolution images in vivo, and was recently reproducibly utilized to visualize transplanted islets. Although successful early vascularization of islet grafts is pivotal for long-term islet survival and function, limited in vivo information is available on the time course of angiogenesis in transplanted islets. We have previously demonstrated a rise of hypoxia-inducible factor (HIF-1a) prior to microscopic evolution of vascularization in murine islet grafts in the early post-transplant period. Moreover, we showed positive effects of pre-transplant culture of islets in nerve growth factor (NGF), and of hyperbaric oxygen therapy (HBO) of recipients, on islet graft survival and function. Angiogenesis can be detected with magnetic resonance imaging (MRI) via change in contrast enhancement of tissue over time. The main hypothesis of this proposal is that dynamic contrast-enhanced (DCE) -MRI can be used for real time assessment of vascularization in transplanted human islets. The specific aims are: 1. To utilize MRI in developing a novel vascularization-focused approach for visualization of transplanted humans islets; 2. To test the relationship between angiogenesis measured by MRI and islet graft survival and function; and 3. To reduce hypoxia-associated beta-cell apoptosis in islet transplantation using a novel combined NGF/HBO strategy monitored by DCE-MRI. The short-term goal is to extend DCE-MRI data on normal and accelerated angiogenesis generated by this proposal to a clinical model of islet transplantation in the imminent future. This would provide an invaluable tool for monitoring islets following transplantation, detecting early changes in islet vasculature, and allowing earlier intervention to salvage and prolong islet graft function. The long-term goal is for DCE-MRI, in combination with other in vivo imaging approaches, to provide a comprehensive non-invasive real time picture of native and transplanted beta-cells, which would ultimately enable the development of a successful cure for type 1 diabetes.

描述（由申请人提供）： 胰岛的体内成像可以提供有关1型糖尿病中内源性和/或移植β细胞生命周期的宝贵信息。当前的体内成像尝试集中在胰岛质量，分泌产物或炎症标志物的量化上。与显微镜相反，磁共振成像（MRI）可以非侵入性地在体内传递高分辨率图像，并且最近可重复用于可视化移植的胰岛。尽管胰岛移植物的成功早期血管形成是长期胰岛存活和功能的关键，但在移植胰岛中血管生成的时间过程中可获得有限的体内信息。先前，我们已经在移植后早期的鼠胰岛移植物中表现出了缺氧诱导因子（HIF-1A）的增加。此外，我们在神经生长因子（NGF）和受体高压氧疗法（HBO）中显示了胰岛生长因子（NGF）的移植前培养物对胰岛移植物存活和功能的积极影响。可以通过磁共振成像（MRI）检测血管生成，通过随着时间的推移的对比增强的变化。该提议的主要假设是动态对比增强（DCE）-MRI可用于实时评估移植的人类胰岛中的血管化。具体目的是：1。利用MRI开发一种新型的以血管化的方法来可视化移植的人类胰岛； 2。测试通过MRI测量的血管生成与胰岛移植物的生存和功能之间的关系；和3。使用DCE-MRI监测的新型NGF/HBO策略在胰岛移植中减少缺氧相关的β细胞凋亡。短期目标是将该提案产生的正常和加速血管生成的DCE-MRI数据扩展到即将来临的胰岛移植的临床模型。这将提供一个无价的工具，用于监测移植后的胰岛，检测胰岛脉管系统的早期变化，并允许早期干预以挽救和延长胰岛移植功能。长期目标是DCE-MRI与其他体内成像方法结合使用，以提供全面的非侵入性实时图片，对本机和移植的β细胞提供，这最终将能够开发1型1型糖尿病的成功疗法。