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Islets Transplanted in Immunoisolation Devices: A Review of the Progress and the Challenges that Remain

机译:胰岛移植到免疫隔离设备中:进展和仍然存在的挑战的回顾

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摘要

The concept of using an immunoisolation device to facilitate the transplantation of islets without the need for immunosuppression has been around for more than 50 yr. Significant progress has been made in developing suitable materials that satisfy the need for biocompatibility, durability, and permselectivity. However, the search is ongoing for a device that allows sufficient oxygen transfer while maintaining a barrier to immune cells and preventing rejection of the transplanted tissue. Separating the islets from the rich blood supply in the native pancreas takes its toll. The immunoisolated islets commonly suffer from hypoxia and necrosis, which in turn triggers a host immune response. Efforts have been made to improve the supply of nutrients by using proangiogenic factors to augment the development of a vascular supply in the transplant site, by using small islet cell aggregates to reduce the barrier to diffusion of oxygen, or by creating scaffolds that are in close proximity to a vascular network such as the omental blood supply. Even if these efforts are successful, the shortage of donor islet tissue available for transplantation remains a major problem. To this end, a search for a renewable source of insulin-producing cells is ongoing; whether these will come from adult or embryonic stem cells or xenogeneic sources remains to be seen. Herein we will review the above issues and chart the progress made with various immunoisolation devices in small and large animal models and the small number of clinical trials carried out to date.
机译:使用免疫隔离装置促进胰岛移植而不需要免疫抑制的概念已经存在了50多年。在开发满足生物相容性,耐久性和渗透选择性需求的合适材料方面已经取得了重大进展。然而,正在寻找一种允许足够的氧气转移,同时保持对免疫细胞的屏障并防止移植组织排斥的装置。将胰岛与天然胰腺的丰富血液供应分开会造成很大的损失。免疫分离的胰岛通常患有缺氧和坏死,进而触发宿主免疫反应。通过使用促血管生成因子来增加移植部位血管供应的发展,使用小的胰岛细胞聚集体以减少氧气扩散的障碍或通过建立紧密的支架,已做出努力来改善营养供应靠近诸如网膜供血的血管网络。即使这些努力是成功的,供体胰岛组织可用于移植的短缺仍然是一个主要问题。为此,正在进行寻找可再生来源的胰岛素产生细胞的研究。它们是否来自成体或胚胎干细胞或异种来源仍有待观察。在此,我们将回顾上述问题,并绘制各种免疫隔离设备在大小动物模型中的进展以及迄今为止进行的少量临床试验的图表。

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