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。其中包括300多万加拿大人，由于若干因素，这些数字正在急剧增加。人们和加拿大医疗保健系统的经济负担是巨大的（每年130亿美元）。在1型和2型糖尿病中都观察到产生胰岛素的细胞（β细胞）的损失。胰岛细胞移植可恢复糖尿病患者所需的大量功能性β细胞，以达到正常血糖水平。然而，这种策略遇到了许多问题，包括缺乏标准的胰岛移植方案，分离后胰岛产量不足以及移植后β细胞凋亡。该项目的长期目标是开发一种能够支持高密度培养用于胰岛素生成的内分泌胰岛的培养室。

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.