SYNTHETIC RGD MATRIX TO SUPPORT ISLET TRANSPLANTATION

超过1600万美国人患有糖尿病，每年报告近75万例。胰岛素依赖型糖尿病最常发生在儿童和年轻人中，在美国有150万例。胰岛素依赖型糖尿病患者不产生胰岛素，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获得完整的、可接受的胰腺的后勤需求，使这不是一个可行的长期解决方案。基于皮肤再生组织工程基质的成功开发和临床应用，Integra Lifesciences Corporation开始研究开发一种新方法，为IDDM患者提供组织工程胰腺。该开发项目将解决以下目标：（1）设计和生产无菌、RGD肽修饰的胶原基质，其将促进猪胰岛的粘附、活力和功能性，（2）优化培养条件，以在植入前最大化细胞功能，以及（3）使用猪模型系统证明最佳植入部位。本I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750，000例新病例（2）。1型糖尿病（胰岛素依赖型糖尿病，IDDM）最常发生在儿童和年轻人中，占肾透析患者的三分之一。胰岛素依赖型糖尿病患者不产生胰岛素，必须每天服用胰岛素才能维持生命。然而，迄今为止，胰岛素还没有成功地消除血糖水平的大幅波动，也没有阻止疾病严重并发症的进展。

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.