Pancreas Transporter Development and Validation

胰腺转运蛋白的开发和验证

基本信息

批准号：
7123761
负责人：
MICHAEL John TAYLOR
金额：
$ 48.95万
依托单位：
CELL AND TISSUE SYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7123761
关键词：
athymic mouse biomedical equipment development clinical biomedical equipment clinical research cold temperature human tissue pancreatic islet transplantation pancreatic islets perfusion swine tissue /organ preservation

项目摘要

DESCRIPTION (provided by applicant): Transplantation of islets of Langerhans for the clinical treatment of Type I diabetes has had a resurgence of interest due to results obtained using the "Edmonton protocol". However, at this time, procurement of donor pancreases for islet isolation and transplantation is in its infancy. Most pancreases at more remote donor sites are not procured due to justified concerns about post-mortem ischemia during transport to the islet isolation and transplant center. Perfusion/preservation technology has been shown to have a major impact in circumventing ischemic injury in kidney transplantation. This proposal seeks to apply this approach to the preservation and procurement of viable islets for transplantation. The primary objective of this proposal is to use state-of-the-art perfusion technology and new preservation solutions to test the hypothesis that machine perfusion can improve the yield and viability of islets prepared from ischemic pancreases. To this end, a prototype pancreas transporter (PTR) was designed and constructed in the Phase I study. The feasibility of 24h perfusion preservation at 2-7¿C was demonstrated using a porcine model that exceeds the 16h documented to be the present clinical limits of safe, static cold storage of donor pancreatic. Islet yield and function was demonstrated to be equivalent to that obtained from fresh control pancreases. The safety and efficacy of this new technology will be further investigated during this Phase II study with three specific aims. The first step will be to implement design modifications to the PTR ensuing from the Phase I feasibility study. The second step will entail a comparison of the yield and function indices for islets isolated from pancreata perfused for 24h on the PTR with indices obtained from control, 24h conventionally stored pancreata. Then the interaction between cold perfusion time (24 and 48h) and warm ischemia time (up to 60 min) on porcine islet isolation parameters will be evaluated for the definition of the potential clinical scope and technology limits. Finally, human pancreases that are unsuitable for transplantation will be employed for pre-clinical validation of this technology. It is anticipated that the availability of a pancreas transporter and pancreas perfusion protocols will permit utilization of most, if not all, pancreases suitable for transplantation in the U.S. Furthermore, the PTR may permit islet isolation banking for long-term storage. Banking would allow time for better HLA matching of donors to recipients, off-the-shelf availability, and enable quality assurance/control procedures to be conducted prior to transplantation. This research program is supported by collaboration with three major clinical centers interested in validation of this perfusion technology for their future use.

描述（通过应用提供）：由于使用“埃德蒙顿方案”获得的结果，兰格汉斯胰岛的胰岛胰岛移植引起了人们的关注。但是，目前，供体胰腺胰腺分离和移植的采购仍处于起步阶段。由于在运输到胰岛隔离和移植中心期间，大多数偏远供体站点的胰腺未得到采购。灌注/保存技术已被证明对肾脏移植中的缺血性损伤产生了重大影响。该提案旨在将这种方法应用于可行胰岛进行移植的准备和采购。该提案的主要目的是使用最先进的灌注技术和新的保存解决方案来检验以下假设：机器灌注可以提高缺血性胰腺制备的胰岛的产量和生存能力。为此，在I期研究中设计和构建了原型胰腺转运蛋白（PTR）。使用猪模型超过16H，这是2-7°C时24小时灌注制备的可行性，该模型超过了16小时，该模型是当前的临床限制，即供体胰腺的安全，静态冷藏。胰岛产量和功能已证明与从新鲜对照胰腺获得的相等。在这项II阶段研究中，将进一步研究这项新技术的安全性和效率。第一步是对I阶段可行性研究的随之而来的PTR实施设计修改。第二步将需要比较从PTR上灌注24h的胰岛的胰岛的产量和功能指标，并从对照中获得的指数24小时，常规存储的胰腺。然后，将评估冷灌注时间（24和48h）与猪胰岛分离参数上温暖的缺血时间（最高60分钟）之间的相互作用，以定义潜在的临床范围和技术限制。最后，将采用不适合移植的人类胰腺来临时验证该技术。预计胰腺转运蛋白和胰腺灌注方案的可用性将允许大多数（如果不是全部）使用适合在美国移植的胰腺，此外，PTR可以允许胰岛隔离银行业务用于长期存储。银行业务将使时间可以更好地匹配捐助者与接收者，现成的可用性，并在移植前实现质量保证/控制程序。该研究计划得到了与有兴趣验证该灌注技术未来使用的三个主要临床中心合作的支持。