Automated System for High Yield Pancreatic Islet Isolation

高产胰岛分离自动化系统

• 批准号: 10373120
• 负责人: Lotien Richard Huang
• 金额: $ 74.04万
• 依托单位: CG SCIENTIFIC, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373120
• 关键词: Adoption; Area; Benchmarking; Biological Models; Biotechnology; Brittle diabetes; Cell Separation; Clinical; Clinical Investigator; Clinical Trials; Data; Development; Diabetes Mellitus; Diabetic mouse; Digestion; Dose; Effectiveness; Engineering; Enzymes; Esthetics; Exhibits; Failure; Family suidae; Glucose; Goals; Head; Health; Human; Human Resources; Insulin-Dependent Diabetes Mellitus; Intervention; Islets of Langerhans; Islets of Langerhans Transplantation; Legal patent; Medical; Medical Device; Medical center; Methods; Morphology; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Outcome; Pancreas; Patients; Performance; Phase; Preparation; Principal Investigator; Process; Publications; Recovery; Research; Research Personnel; Science; System; Targeted Research; Technology; Total Pancreatectomy; Translating; Transplantation; Work; base; chronic pancreatitis; commercialization; cost; cost effective; effective therapy; experience; improved; in vivo; insulin secretion; islet; microfluidic technology; mouse model; novel; preclinical efficacy; prevent; prototype; standard of care; success; tool

Project Summary/Abstract This Phase II project aims to develop an automated system for high-yield pancreatic islet isolation for use in islet transplantation (an emerging therapy for type 1 diabetes) and diabetes research. The effectiveness of islet transplantation relies critically on the quality and quantity of the transplanted islets, which are isolated from deceased human donor pancreata. However, the current method for islet isolation is highly user-dependent, provides low numbers of islets, and suffers close to 50% process failure rates. These drawbacks necessitate the frequent use of many donor pancreata and multiple transplants per patient to achieve good outcomes, making islet transplantation highly inefficient and cost- prohibitive. The lack of a reliable and easy-to-use tool for islet isolation also precludes many researchers from obtaining high-quality islets for their research. To overcome these limitations, CG Scientific is developing a patent-pending “automated cell isolation platform” (ACIP) technology to create an automated system for islet isolation. The technology has a unique configuration to (1) enable efficient enzyme digestion, (2) automate the isolation process in a closed-system format, and (3) break through limitations that prevent current methods from achieving high islet recovery and viability. Using porcine pancreata as a model system in Phase I, the company has demonstrated successful islet isolation, with ~2.4x higher islet recovery compared to the current method and an unmatched islet viability of ~95% on average. The islets exhibit outstanding morphology and glucose-stimulated insulin secretion function. The automated system will potentially eliminate user-related process failure and render single-donor islet transplantation highly efficacious―using only one donor pancreas and one transplant per recipient―with up to 80% cost reduction. In Phase II, the investigator team will (1) develop a fully functional product prototype, (2) optimize the performance of the automated prototype for both human and porcine islets, (3) benchmark superior islet isolation capabilities compared to the current method, and (4) demonstrate the pre-clinical efficacy of the resulting islets for diabetes reversal using a mouse model. This Phase II project will generate significant data and know-how for (1) transitioning to manufacturing, (2) obtaining regulatory approval, and (3) product commercialization. The investigator team includes medical device experts, islet biologists, engineers, and medical doctors who specialize in clinical islet manufacturing and transplantation. The success of this project will result in the commercialization of an essential tool that will not only make single-donor islet transplantation highly effective, affordable, and available, but also accelerate a wide range of diabetes research―thereby benefiting the many patients around the world who suffer from diabetes.

项目摘要/摘要 该第二阶段项目旨在开发一种用于高收益胰岛隔离的自动化系统 用于胰岛移植（1型糖尿病的新兴疗法）和糖尿病研究。这 胰岛移植的有效性主要依赖于移植胰岛的质量和数量， 与已故的人类供体胰腺隔离。但是，胰岛的当前方法 隔离是用户高度依赖性的，提供的胰岛数量很少，并且遭受接近50％的过程 故障率。这些缺点经常使用许多供体胰腺和多个供体 每位患者的移植物以取得良好的结局，使小岛移植高效且成本高 过敏。缺乏可靠且易于使用的胰岛隔离工具，也排除了许多研究人员 从获得其研究的高质量胰岛。为了克服这些局限性，CG科学是 开发申请专利的“自动细胞隔离平台”（ACIP）技术，以创建 胰岛隔离的自动化系统。该技术具有（1）启用高效的独特配置 酶消化，（2）以封闭系统格式自动化隔离过程，（3）突破 阻止当前方法实现高胰岛恢复和生存能力的局限性。使用猪 胰腺是第一阶段的模型系统，该公司已证明了成功的胰岛隔离，并具有 与当前方法和无与伦比的胰岛可行性相比，iSlet回收率高约2.4倍。 平均的。胰岛暴露了杰出的形态和葡萄糖刺激的胰岛素分泌功能。 自动化系统可能会消除用户相关的过程故障并渲染单次胰岛 移植高效地使用一个供体胰腺，每个受体中的一个移植 高达80％的成本降低。在第二阶段，研究人员团队将（1）开发功能齐全的产品 原型，（2）优化人类和猪胰岛自动化原型的性能， （3）与当前方法相比，基准高胰岛隔离能力，（4）证明 使用小鼠模型逆转糖尿病的胰岛的临床前效率。该阶段II 项目将生成重要的数据和（1）过渡到制造的知识，（2）获得 监管批准和（3）产品商业化。调查员团队包括医疗设备 专门从事临床胰岛制造和专业的专家，生物学家，工程师和医生 移植。该项目的成功将导致商业化的基本工具， 不仅将使单单胰岛移植高效，负担得起且可用，而且还将 加速广泛的糖尿病研究 - 从而使世界上许多患者受益 患有糖尿病的人。