SYNTHETIC RGD MATRIX TO SUPPORT ISLET TRANSPLANTATION

支持胰岛移植的合成 RGD 基质

• 批准号: 6013220
• 负责人: MICHAEL D PIERSCHBACHER
• 金额: $ 13.38万
• 依托单位: TELIOS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6013220
• 关键词: antiseptic sterilization; artificial membranes; biomaterial development /preparation; cell adhesion molecules; collagen; diabetes mellitus therapy; extracellular matrix; guinea pigs; histology; immunocytochemistry; insulin dependent diabetes mellitus; integrins; medical implant science; pancreatic islet transplantation; peptide chemical synthesis; peptides; swine; tissue engineering; tissue support frame

More than 16 million Americans have diabetes and nearly 750,000 cases are reported every year. Insulin Dependent Diabetes Mellitus occurs most often in children and young adults and accounts for 1.5 million cases in the United States. IDDM patients do not produce insulin and must take daily insulin to stay alive. The critical shortage of donor organs coupled to the logistic demands of having an intact, acceptable pancreas available at a precise time and location, does not make this a feasible long-range solution. Based on the successful development and clinical use of a tissue engineered matrix for skin regeneration, Integra Lifesciences Corporation initiated studies to develop a novel approach to providing a tissue engineered pancreas for patients with IDDM. This development program will address the following objectives (1) the design and production of a sterile, RGD peptide-modified collagen matrix that will promote the adhesion, viability, and functionality of porcine islets, (2) the optimization of the culture conditions to maximize cell functionality prior to implantation, and (3) the use of a porcine model system to demonstrate the best implantation site. The purpose of this Phase I application is to establish the feasibility of producing a manufacturable, sterile product that will have a commercially viable impact on the survival and function of transplanted pancreatic islets. PROPOSED COMMERCIAL APPLICATIONS: On 1997, the annual direct and indirect costs of type I and II diabetes mellitus were estimated at 98.2 billion which represents about 10 percent of the total personal health care expenditure in the United States (1). More than 16 million Americans have diabetes and nearly 750,000 new cases are reported every year (2). Type 1 diabetes (insulin Dependent Diabetes Mellitus, IDDM) occurs most often in children and young adults and accounts for one-third of renal dialysis patients. IDDM patients do not produce insulin and must take daily insulin to stay alive. To date, however, insulin has not succeeded in eliminating the wide swings in blood glucose levels nor has it prevented the progression of serious complications of the disease.

超过 1600 万美国人患有糖尿病，每年报告近 75 万例病例。胰岛素依赖性糖尿病最常发生在儿童和年轻人中，在美国有 150 万例。 IDDM 患者不能产生胰岛素，必须每天服用胰岛素才能维持生命。供体器官的严重短缺，加上在精确的时间和地点提供完整的、可接受的胰腺的后勤需求，并不能使这成为一个可行的长期解决方案。基于用于皮肤再生的组织工程基质的成功开发和临床应用，Integra Lifesciences Corporation 启动了研究，开发一种为 IDDM 患者提供组织工程胰腺的新方法。该开发计划将实现以下目标 (1) 设计和生产无菌、RGD 肽修饰的胶原蛋白基质，以促进猪胰岛的粘附、活力和功能，(2) 优化培养条件以最大限度地提高猪胰岛的粘附性、活力和功能性。植入前的细胞功能，以及（3）使用猪模型系统来证明最佳植入位点。该一期申请的目的是确定生产可制造的无菌产品的可行性，该产品将对移植胰岛的存活和功能产生商业上可行的影响。拟议的商业应用： 1997 年，I 型和 II 型糖尿病的年度直接和间接费用估计为 982 亿美元，约占美国个人医疗保健总支出的 10% (1)。超过 1600 万美国人患有糖尿病，每年报告近 75 万例新病例 (2)。 1 型糖尿病（胰岛素依赖性糖尿病，IDDM）最常见于儿童和年轻人，占肾透析患者的三分之一。 IDDM 患者不能产生胰岛素，必须每天服用胰岛素才能维持生命。然而，迄今为止，胰岛素尚未成功消除血糖水平的大幅波动，也未能阻止疾病严重并发症的进展。