EXPANSION OF PANCREATIC ISLETS USING A NOVEL BIOMATERIAL

描述(改编自《调查者摘要》)：糖尿病(类型 1)影响全球超过1亿人，约150万人 在美国，这种疾病导致直接的医疗和间接的非医疗 高达100亿美元的成本(如残疾、过早死亡) 每年一次。人类胰岛移植的临床试验表明， 逆转糖尿病的可行性。然而，有两个主要问题(免疫排斥 和数量不足的胰岛)限制了其作为标准的使用 治疗。原代异种组织(例如，来自猪的)提供了潜在的 克服了可移植组织的短缺，但存在额外的风险， 例如人畜共患病的传播。另一种方法涉及 胰岛在培养中的体外扩增。调查人员最近发现 胰岛与一种新的生物材料的联合培养 肠粘膜下层(SIS)：(1)增加胰岛质量，(2)增加胰岛 胰岛素对葡萄糖的反应，(3)增加胰岛胰岛素含量，以及 (4)诱导胰岛细胞增殖核抗原。总而言之， 这些数据表明，SIS中的一个或多个组件导致了胰岛，特别是 β细胞，体外增殖。这个项目的第一阶段发现 提取的但未溶解的SIS可引起胰岛的增殖。在阶段中 I，调查人员能够细化加工方法，将SIS提取到 允许有胰岛增殖活性的标准化制剂。在这 第二阶段申请调查人员建议使用所获得的信息 在第一阶段开发两个新产品：(1)基于SIS的组织培养基 用于胰岛的体外增殖，以及(2)一种复合生物材料 SIS-可以作为真皮移植物移植的胰岛(尤其是 糖尿病溃疡的治疗)或血管移植(用于全身治疗)。 调查人员得到了库克生物技术公司的支持，他们将担任他们的 这两种产品的第三阶段合作伙伴。这些产品将拥有 加强胰岛移植作为治疗和/或治愈糖尿病的重要性 I型糖尿病。 建议的商业应用： 不可用

DESCRIPTION (Adapted from the Investigator's Abstract): Diabetes mellitus (Type 1) affects over 100 million individuals worldwide and approximately 1.5 million in the U.S. This disease results in direct medical and indirect non-medical costs (e.g., disability, premature mortality) of as much as 10 billion dollars annually. Clinical trials of human islet transplantation have demonstrated the feasibility of reversing diabetes. However, two major problems (immunorejection and an insufficient quantity of islets) have limited its use as a standard treatment. Primary xenograft tissue (e.g., from pigs) offers the potential to overcome the shortage of transplantable tissue, but presents additional risks, such as the transmission of zoonotic disease. Another approach involves the in vitro expansion of islets in culture. The investigators have recently shown that co-culture of islets with a novel biomaterial derived from the small intestinal submucosa (SIS): (1) increases islet mass, (2)increases islet insulin response to glucose, (3)increases the islet insulin content, and (4)induces proliferating cell nuclear-antigen on islet cells. Collectively, these data suggest that one or more components in SIS cause islet, specifically Beta cell, proliferation in vitro. The phase I stage of this project found that extracted, but not solubilized SIS elicited islet proliferation. During Phase I, the investigators were able to refine processing methods to extract SIS to allow a standardized preparation with islet proliferating activity. In this Phase II application the investigators propose to use this information gained in Phase I to develop two novel products: (1) an SIS based tissue culture media for in vitro proliferation of islets, and (2) a composite biomaterial of SIS-islets which can be transplanted as either a dermal graft (especially for the treatment of diabetic ulcers) or a vascular graft (for systemic treatment.) The investigators have support from Cook Biotech, Inc. who will serve as their Phase III partner for both of these products. These products will have importance in enhancing islet transplantation as a treatment and/or cure for type I diabetes. PROPOSED COMMERCIAL APPLICATION: Not available