Engineering of a Perfusion Chamber for High-Density Cultures of Endocrine Pancreatic Islets for Insulin Production

2010年，国际糖尿病联合会估计全球有2.85亿人患有糖尿病。这包括300多万加拿大人，由于一些因素，这一数字正在急剧增加。人们和加拿大医疗系统的财政负担是巨大的(130亿美元/年)。在1型和2型糖尿病中都观察到了胰岛素产生细胞(β细胞)的丧失。胰岛细胞移植可以恢复糖尿病患者达到正常血糖所需的功能β细胞数量。然而，这一策略遇到了许多问题，包括标准的胰岛移植方案不可用，分离后胰岛产量不足，移植后β细胞凋亡。该计划的长期目标是开发一个小室，以支持高密度培养内分泌胰岛以生产胰岛素。 其预期的意义和新颖性是：1)由于胰岛在隔离过程中自然环境受到了破坏，因此更好地了解它们与环境的相互作用可以改进隔离程序，从而改善胰岛的存活和功能。我们的仿生表面提供了出色的低污染涂层，允许通过消除非特定细胞响应来仅研究特定细胞响应。这对于区分影响小岛行为的原因是必要的。2)了解流体流动状况如何影响胰岛和β细胞反应，对于更好地确定移植胰岛如何受到植入部位流动状况的影响是至关重要的，因为这样的知识是不可用的。我们的灌流生物反应器是少数几个允许进行此类模型研究以精确确定最佳流动条件以改善胰岛存活和功能的反应器之一。3)最后，关于如何在孤立的胰岛中重建有功能的血管系统，人们知之甚少。血管重建化是维持胰岛生存和功能所必需的。我们会研究这方面的问题。总体而言，这项研究计划将产生关键的科学论文和专利，创造知识和成果技术转让。它还将有助于培养高素质的人才。

In 2010, the International Diabetes Federation estimated that 285 millions people worldwide have diabetes. This includes more than three millions Canadians, and these numbers are increasing dramatically owing to a number of factors. The financial burden on people and on the Canadian healthcare system is enormous ($13 billion/year). The loss of insulin-producing cells (beta cells) has been observed in both type 1 and type 2 diabetes. Pancreatic islet cell transplantation can restore the required mass of functional beta-cells to achieve normoglycemia in diabetics. However, this strategy has encountered many problems including the unavailability of a standard islet transplant protocol, insufficient islet yields after isolation and beta-cell apoptosis following transplantation. The LONG-TERM PROGRAM OBJECTIVE is to develop a chamber to support a high-density culture of endocrine pancreatic islets for insulin production. The ANTICIPATED SIGNIFICANCE AND NOVELTY is: 1) Because the native environment of the islets has been damaged during isolation, a better understanding of their interactions with their environment could improve isolation procedures and therefore islet survival and function. Our biomimetic surfaces provide excellent low-fouling coatings allowing studying only specific cell responses by eliminating non-specific ones. This is necessary to discriminate the causes affecting the islet behavior. 2) Understanding how fluid flow conditions affect islet and beta-cell responses is essential to better identify how transplanted islets are affected by flow conditions encountered at an implantation site because such knowledge is not available. Our perfusion bioreactor is one of the few that allows carrying out such model studies to pinpoint optimal flow conditions to improve islet survival and function. 3) Finally, little is known about how to re-establish a functional vasculature in isolated islets. Vascularization is mandatory to sustain islet survival and function. This aspect will be studied. Overall, this research program will result in key scientific papers and patents creating knowledge and yielding technology transfer. It will also contribute to train highly qualify personnel.