Recovery /preservation of donation cardiac death livers

心脏死亡捐献肝脏的恢复/保存

• 批准号: 7052654
• 负责人: MARK G CLEMENS
• 金额: $ 20.55万
• 依托单位: HEPATOSYS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052654
• 关键词: cold temperature; isolation perfusion; liver cells; liver function; liver preservation; liver transplantation; male; nonhuman therapy evaluation; perfusion; respiratory oxygenation; swine; technology /technique development; tissue donors; vascular endothelium

DESCRIPTION (provided by applicant): The long term goals of this project is to increase the number of Donation after Cardiac Death (DCD) livers available for transplantation by developing a clinically relevant hypothermic machine perfusion (HMP) method for recovery and preservation. Currently, DCD livers are transplantable and have the potential to increase the donor pool 20-40%. However, they are largely under utilized due to poor preservation by the current method of simple cold storage (SCS). HMP has been shown to improve recovery and preservation of DCD kidneys, but this technology has not been successfully transferred to the liver. Studies show that HMP can improve graft survival in animal models. In addition, oxygenation during HMP improved functional recovery suggesting the importance of restoring tissue energy stores. The goal of this Phase I STTR is to test the feasibility of HMP to recover and preserve DCD livers in the porcine model by accomplishing the following Specific Aims: 1) Scale-up current HMP system for large animal studies and 2) compare post-storage function of porcine livers in an isolated perfusion system following 10 hour preservation for 3 groups, 1) heart-beating + SCS, 2) DCD (30min WI) + SCS, and 3) DCD (30min WI) + HMP. The scale-up system will include oxygenation and dual flow controlled perfusion to the portal vein and hepatic artery to improve flow homogeneity. Functional recovery will be evaluated in an isolated perfusion system which allows greater control and assessment with a broad spectrum of endpoints. Hepatocellular and endothelial functions and damage will be assessed by bile production, indocyanine green secretion, hyaluronic acid uptake, tissue energy state, oxygen consumption, histology, and release of enzymes. This system can assess whether grafts experience primary non-function, a major cause of failure in DCD organs. The success of this project will be directly related to the establishment of a critical partnership between the team of transplant surgeons, the scientists and biomedical engineers who will collaboratively test and modify as needed the procedure for preserving DCD livers. This project will form the basis for further testing in a Phase II STTR application for recovery and preservation of DCD livers in a clinically relevant transplant model. Future plans include joint projects with Organ Recovery Systems (a developer of a liver transplant device) to combine technologies to develop a viable device and protocol to recover and preserve DCD livers.

描述(由申请人提供)：该项目的长期目标是通过开发临床相关的低温机器灌注(HMP)恢复和保存方法来增加心脏死亡(DCD)后可供移植的肝脏的捐赠数量。目前，DCD肝脏是可移植的，并有可能 增加20%-40%的捐赠者。然而，由于目前的方法保存不佳，它们在很大程度上没有得到充分利用 简单冷藏(SCS)。HMP已被证明可以改善DCD肾脏的恢复和保存，但这项技术尚未成功转移到肝脏。研究表明，HMP可以提高动物模型移植物的存活率。此外，HMP期间的氧合改善了功能恢复，表明恢复组织能量储存的重要性。第一阶段的目标是在猪模型上测试HMP恢复和保存DCD肝脏的可行性，以实现以下特定目标：1)扩大现有HMP系统的规模 动物研究和2)比较猪肝在隔离灌流系统中10小时后的保存功能 保存3组，1)心脏跳动+SCS组，2)DCD(30min加权像)+SCS组，3)DCD(30min加权像)+HMP组。放大系统将包括充氧和门静脉和肝动脉的双流量控制灌流，以改善血流均匀度。功能恢复将在隔离的灌流系统中进行评估，该系统允许通过广泛的终点进行更好的控制和评估。通过胆汁生成、吲哚青绿分泌、透明质酸摄取、组织能量状态、耗氧量、组织学和酶的释放来评估肝细胞和内皮的功能和损伤。这个系统可以评估移植物是否经历了原发无功能，这是DCD器官失败的主要原因。这个项目的成功将直接关系到该项目的建立 这是移植外科医生团队、科学家和生物医学工程师之间的关键合作伙伴关系，他们将根据需要合作测试和修改保存DCD肝脏的程序。该项目将为在临床相关移植模型中恢复和保存DCD肝脏的第二阶段STTR应用程序的进一步测试奠定基础。未来的计划包括与器官恢复系统公司(一家肝脏移植设备的开发商)联合开展项目，结合技术开发可行的设备和方案，以恢复和保存DCD肝脏。