BIOACTIVE POLYMERS FOR EFFECTIVE ISLET DELIVERY SYSTEM

用于有效胰岛输送系统的生物活性聚合物

• 批准号: 6350743
• 负责人: You Han Bae
• 金额: $ 23.36万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6350743
• 关键词: biomaterial evaluation; cell proliferation; cytoprotection; diabetes mellitus therapy; drug delivery systems; high performance liquid chromatography; hybrid cells; insulin; laboratory rat; longevity; oxygen transport; packaging material; pancreatic islet function; pancreatic islet transplantation; polymers

The goals of this application are to improve the functionality (insulin secretion rate and pattern) and to expand the life-span of immunoprotected pancreatic islets. The low functionality (less than 15% of the insulin release rate of native islets in pancreas) required a large number of islets within the implant, which causes complications in surgery and discomfort for patients. The limited life-span of the islets in a biohybrid artificial pancreas (BAP) may require frequent cell reseeding and cause further supply problems in islet transplantation. Improved islet functionality and prolonged life-span will minimize the volume of the BAP by reducing the number of islets needed for diabetic patients to achieve normoglycaemia and reduce probes associated with islet supply. It is hypothesized in this research that 1) my mimicking facilitated oxygen transport in avascular tissues, the immunoprotected islets release a higher amount of insulin, recover their intrinsic biphasic release pattern, and prolong their life-span, and 2) insulinotropic agents further promote insulin secretion from islets. Based on these hypotheses, a new BAP system will be designed which contains the water-soluble polymeric conjugates of oxygen carriers (or oxygen binding vesicles) and islet stimulants of sulfonylurea compounds and glucagon-like insulinotropic peptide-1 with entrapped islets in the BAP. The research examines their effects on islet viability, the amount of insulin secretion, the insulin release profile, and the life-span of immunoprotected pancreatic islets. Especially, the combined synergy effects of both hypotheses will be emphasized. The successful results in improving functionality and life-span of islets entrapped in an immunoprotected membrane can be applied in the delivery of micro-encapsulated therapeutic cells and to the miniaturization of a BAP. In addition, the approaches proposed in this research will provide a potential solution to the shortage problem of human cell or tissue sources.

本应用的目的是改善功能（胰岛素分泌速率和模式）和延长免疫保护胰岛的寿命。低功能（胰腺中天然胰岛胰岛素释放率不到15%）需要植入大量胰岛，这导致手术并发症和患者不适。生物杂交人工胰腺（BAP）中胰岛的有限寿命可能需要频繁的细胞补种，并在胰岛移植中引起进一步的供应问题。胰岛功能的改善和寿命的延长将通过减少糖尿病患者实现正常血糖所需的胰岛数量和减少与胰岛供应相关的探针来减少BAP的体积。本研究假设：1)模拟促进了无血管组织中的氧运输，免疫保护的胰岛释放更多的胰岛素，恢复其固有的双相释放模式，延长其寿命；2)促胰岛素药物进一步促进胰岛分泌胰岛素。基于这些假设，将设计一种新的BAP系统，该系统包含氧载体（或氧结合囊泡）的水溶性聚合物偶联物、磺酰脲类化合物的胰岛刺激物和胰高血糖素样胰岛素性肽-1，并将胰岛包裹在BAP中。该研究考察了它们对胰岛活力、胰岛素分泌量、胰岛素释放谱和免疫保护胰岛寿命的影响。特别强调两种假设的联合协同效应。这一成功的结果改善了免疫保护膜包裹胰岛的功能和寿命，可以应用于微囊化治疗细胞的递送和BAP的小型化。此外，本研究提出的方法将为解决人类细胞或组织来源短缺问题提供潜在的解决方案。