IMMUNOISOLATION BIOCAPSULES FOR PANCREATIC ISLET CELLS

用于胰岛细胞的免疫隔离生物胶囊

• 批准号: 6212793
• 负责人: FRANCIS J MARTIN
• 金额: $ 9.68万
• 依托单位: IMEDD, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-20 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6212793
• 关键词: extracellular matrix; insulin; pancreatic islets; secretion; technology /technique development; tissue /cell culture; tissue /cell preparation

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.

该计划的长期目标是开发能够在体内保护一系列分泌细胞而不需要免疫抑制的装置。该计划的最初重点是开发微制造的“生物胶囊”，由高度控制的微架构组成，在生理相关的尺度（纳米至微米尺寸）的胰岛细胞。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。本申请具体涉及成功开发含有胰岛的可植入免疫隔离装置的几个关键领域，用于调节1型糖尿病患者的血糖水平。本发明的具体目标如下：1）制造三种预定孔径的无机生物载体组件（12、18和24 nm），用猪胰岛装载半个胶囊，并将两个半个胶囊粘合在一起; 2）在重复的动态条件下测量来自三种孔径的生物囊包封的胰岛细胞的胰岛素释放动力学，直到响应显著降低（从初始水平的30至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;和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型糖尿病以及大部分2型糖尿病患者。1型糖尿病患者约有50万人，2型糖尿病患者几乎是1型糖尿病患者的10倍。因此，大量患者人群可用于治疗。在患者的余生中，该系统每年至少需要更换三到四次。

项目成果

Diffusion characteristics of microfabricated silicon nanopore membranes as immunoisolation membranes for use in cellular therapeutics.

微加工硅纳米孔膜作为免疫隔离膜用于细胞治疗的扩散特性。

• DOI: 10.1089/dia.2005.7.151
• 发表时间: 2005
• 期刊: Diabetes technology & therapeutics
• 影响因子: 5.4
• 作者: Smith,Catherine;Kirk,Randy;West,Teri;Bratzel,Marsha;Cohen,Michael;Martin,Francis;Boiarski,Anthony;Rampersaud,ArfaanA
• 通讯作者: Rampersaud,ArfaanA