IMMUNOISOLATION BIOCAPSULES FOR PANCREATIC ISLET CELLS

该计划的长期目标是开发能够保护体内一系列激素分泌细胞的设备，而不需要免疫抑制。该计划最初的重点是为胰岛细胞开发由高度可控的生理规模(纳米到微米尺寸)的微结构组成的微制“生物胶囊”。10-30 nm的均匀孔径允许宿主(患者)和植入细胞之间交换营养物质、废物和分泌的胰岛素。这项申请特别针对几个关键领域，成功开发了一种含有胰岛的植入式免疫隔离设备，用于调节1型糖尿病患者的血糖水平。这项建议的具体目的如下：1)制造三种预定孔径(12，18和24 nm)的无机生物胶囊成分，将猪胰岛装载到半胶囊中，并将两半粘合在一起；2)在重复动态条件下，测量三种孔径生物胶囊包裹的胰岛细胞的胰岛素释放动力学，直到响应显著降低(初始水平的30-40%)；3)研究两种细胞外基质材料(胶原和Matrigel)对胰岛素释放动力学和胰岛存活的影响；以及4)在体外胰岛素释放研究结束时评估细胞活力。拟议的商业应用：一旦成功开发，该产品将用于治疗1型糖尿病患者以及相当一部分2型糖尿病患者。大约有50万1型糖尿病患者，而2型糖尿病患者的数量几乎是前者的十倍。因此，有大量的患者可供治疗。在患者的余生中，该系统每年至少需要更换三到四次。

The long-term goals of the program are to develop devices capable of protecting a range of hormone-secreting cells in vivo without the need for immunosuppression. The initial focus of the program is development of microfabricated 'biocapsules' composed of highly controlled microarchitectures at physiologically relevant scales (nanometer to micron sizes) for pancreatic islet cells. The 10-30 nm uniform pore sizes allow the exchange of nutrients, waste products, and secreted insulin between host (patient) and implanted cells. This application specifically addresses several key areas for successful development an implantable immunoisolation device containing pancreatic islets for regulation of blood glucose levels in Type 1 diabetes. The following are the specific aims of this proposal: 1) manufacture inorganic biocapsule components at three predetermined pore sizes (12,18, and 24 nm), loading half capsules with porcine islets, and bonding the two halves together; 2) measure insulin release kinetics from biocapsule-encapsulated islet cells from three pore sizes under repeated dynamic conditions until the response is markedly reduced (30 to 40% from initial levels); 3) investigate the effect of two extracellular matrix materials (collagen and Matrigel) on insulin release kinetics and islet survival; and 4) assess cell viability at the end of the in vitro insulin release studies. PROPOSED COMMERCIAL APPLICATIONS: Once successfully developed, this product would be used to treat type-1 diabetics as well as a significant portion of type-2 diabetics. There are about 500,000 type 1 diabetics and nearly ten times as many type-2 diabetics. Thus, a large patient population is available for treatment. The system would need to be replaced at least three to four times a year for the remainder of the patients life.