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世界有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，这些数字正在急剧增加。对人民和加拿大医疗保健系统的财政负担是巨大的（130亿美元/年）。在1型和2型糖尿病中均观察到胰岛素产生细胞（β细胞）的损失。胰岛细胞移植可以恢复所需的功能性β细胞的质量，以实现糖尿病患者的正常血糖。然而，这种策略遇到了许多问题，包括标准胰岛移植方案的不可用性、分离后胰岛产量不足以及移植后β细胞凋亡。长期目标是开发一种支持高密度培养内分泌胰岛以产生胰岛素的培养箱。 预期的意义和新奇是：1）由于胰岛的天然环境在分离过程中被破坏，更好地了解它们与环境的相互作用可以改善分离过程，从而改善胰岛的存活和功能。我们的仿生表面提供了优异的低污染涂层，允许通过消除非特异性的细胞反应来研究特定的细胞反应。这对于区分影响胰岛行为的原因是必要的。2)了解流体流动条件如何影响胰岛和β细胞反应对于更好地确定移植的胰岛如何受到植入部位遇到的流动条件的影响至关重要，因为这些知识不可用。我们的灌注生物反应器是少数几个允许进行此类模型研究以确定最佳流动条件以改善胰岛存活和功能的生物反应器之一。3)最后，关于如何在分离的胰岛中重建功能性脉管系统知之甚少。血管化是维持胰岛存活和功能的必要条件。将研究这方面的问题。总的来说，这项研究计划将产生关键的科学论文和专利，创造知识和产生技术转让。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.