关键词: cryoprotectants islet banking islet cryopreservation islet vitrification pancreatic islets rat islets vitrification

来  源:   DOI:10.4161/org.5.3.9812   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Transplantation of pancreatic islets for the treatment of diabetes mellitus is widely anticipated to eventually provide a cure once a means for preventing rejection is found without reliance upon global immunosuppression. Long-term storage of islets is crucial for the organization of transplantation, islet banking, tissue matching, organ sharing, immuno-manipulation and multiple donor transplantation. Existing methods of cryopreservation involving freezing are known to be suboptimal providing only about 50% survival. The development of techniques for ice-free cryopreservation of mammalian tissues using both natural and synthetic ice blocking molecules, and the process of vitrification (formation of a glass as opposed to crystalline ice) has been a focus of research during recent years. These approaches have established in other tissues that vitrification can markedly improve survival by circumventing ice-induced injury. Here we review some of the underlying issues that impact the vitrification approach to islet cryopreservation and describe some initial studies to apply these new technologies to the long-term storage of pancreatic islets. These studies were designed to optimize both the pre-vitrification hypothermic exposure conditions using newly developed media and to compare new techniques for ice-free cryopreservation with conventional freezing protocols. Some practical constraints and feasible resolutions are discussed. Eventually the optimized techniques will be applied to clinical allografts and xenografts or genetically-modified islets designed to overcome immune responses in the diabetic host.
摘要:
广泛预期用于治疗糖尿病的胰岛移植一旦发现预防排斥的手段而不依赖于整体免疫抑制,最终将提供治愈。胰岛的长期储存对于移植的组织至关重要,胰岛银行,组织匹配,器官共享,免疫操作和多供体移植。已知涉及冷冻的现有冷冻保存方法是次优的,仅提供约50%的存活率。使用天然和合成的冰阻断分子对哺乳动物组织进行无冰冷冻保存的技术的发展,玻璃化过程(形成玻璃而不是结晶冰)是近年来研究的焦点。这些方法已经在其他组织中建立了玻璃化可以通过规避冰诱导的损伤来显著提高存活率。在这里,我们回顾了影响胰岛冷冻保存的玻璃化方法的一些潜在问题,并描述了一些将这些新技术应用于胰岛长期储存的初步研究。这些研究旨在使用新开发的培养基优化玻璃化前低温暴露条件,并将无冰冷冻保存的新技术与常规冷冻方案进行比较。讨论了一些实际的制约因素和可行的解决方案。最终,优化的技术将应用于临床同种异体移植物和异种移植物或旨在克服糖尿病宿主中的免疫反应的遗传修饰的胰岛。
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