Innovating Organ Shipment by Studying Environmental Factors which Affect Organs During Cold Preservation

研究冷藏过程中影响器官的环境因素，创新器官运输

基本信息

批准号：
10689394
负责人：
Joseph R. Scalea
金额：
$ 18.88万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10689394
关键词：
ANXA5 gene Actins Address Affect Air Aircraft Animal Model Animals Annexins Apoptosis Architecture Atmospheric Pressure Biopsy Cardiac Myocytes Cardiac Output Caring Cell Adhesion Cell Adhesion Molecules Cell Death Clinical Cryopreservation Data Data Reporting Devices Dimensions E-Selectin Environment Environmental Impact Environmental Risk Factor Exposure to F-Actin Failure Future Goals Graft Survival Heart Heart Transplantation Helicopter Hemolysis Histology Hospitals Hour Human Immune response Immunologics Improve Access In Situ Nick-End Labeling In Vitro Individual Intercellular adhesion molecule 1 Investigation Ischemia Laboratories Learning Liver Measurement Measures Mediating Methods Modality Modeling Monitor Mus Muscle Cells Organ Organ Survival Organ Transplantation Organ failure Outcome Outcome Measure Process Publications Reporting Research Personnel Risk Shipping Ships Stains Stroke Volume Suggestion Survival Rate System Telemetry Temperature Thrombosis Thrombus Time Transplantation Transportation Trauma Travel Vascular Cell Adhesion Molecule-1 Vertebral column Wing Work experimental study extracellular foot graft function heart function improved innovation natural hypothermia novel organ allocation pressure primary outcome secondary outcome standard of care transplant model vibration

项目摘要

Abstract: There is an urgent and critical need to innovate shipment methods for human organs. While much has been done in the last three decades to improve transplant survival rates and immunologic outcome, little has been done to understand how to optimally care for organs during shipment. As the field of transplantation smartly rethinks organ allocation, more work needs to be done to help improve the process of organ shipment. In prior work, we questioned if on-demand organ shipment with unmanned aircraft, or drones, might improve access to transplantable organs. Organ drones may decrease CIT and improve organ availability. During initial drone experiments, novel telemetry devices showed significant differences in the pressure, temperature, and when drone flight was compared with traditional fixed wing flight. This is particularly interesting because recent publications have revealed differences in organ transplant outcome when organs are moved by air versus ground. Further, it is well known that low-pressure exposure from airline flight negatively impact organ function after trauma. There are no studies addressing these factors or their impact on transplantable organs. We then modeled environmental factors affecting organs in a small model of heterotopic cardiac transplant model. We found that mid-range vibration led to reduced survival when compared with non-vibrated hearts. Explanted hearts showed increases in apoptosis and F-actin derangement. More work is needed to determine the most appropriate way to care for organs in transit and mitigate potential risks during shipment. This proposal builds on our expertise with innovating organ shipment. We hypothesize that CIT is comprised of more than just time alone, and that environmental factors may impact graft survival. We will separate pressure, temperature, and vibration to learn how each factor individually affects transplanted organs with the greater goal of implementing strategies to mitigate each of these risks and improve organ function. In Aim 1 we will determine, presently unmeasured, actual environmental factors that affect hearts during transport by car, helicopter, airplane, and drone. We will calculate temperature, pressure, and vibration, and compare telemetry findings for each shipment modality. We will then assess pre-and-post shipment biopsies for changes cellular adhesion molecules (ICAM-1, VCAM-1) and cytoskeletal actin. In Aim 2, we will model these forces in an animal model of heart transplant. Donor hearts will be pre-treated with pressure, temperature, or vibration. The primary outcome measure will be graft survival. The secondary outcome measure will be non- invasive transthoracic echocardiographic and histology for adhesion molecules and actin as in Aim 1. Here, we will learn for the first time how the environment has been affecting thousands of human organs during shipment. We will then learn how each component of a multi-variable cold ischemia time contributes to organ function, immunological response, and graft survival. Together these findings will launch the field of organ perseveration into the next decade.

摘要：创新人体器官运输方式迫在眉睫。虽然很多在过去的三十年里，人们在提高移植存活率和免疫结果方面所做的工作很少目的是了解如何在运输过程中最佳地护理器官。作为移植领域聪明地重新思考器官分配，需要做更多的工作来帮助改善器官运输流程。在之前的工作中，我们质疑用无人机按需运送器官是否可能改善可移植器官的获取。器官无人机可以降低 CIT 并提高器官可用性。在最初的无人机实验中，新型遥测设备显示出压力、温度，以及无人机飞行与传统固定翼飞行的比较。这一点特别有趣因为最近的出版物揭示了当器官被移动时器官移植结果的差异空气与地面。此外，众所周知，航空飞行中的低压暴露会对器官产生负面影响创伤后的功能。目前还没有研究探讨这些因素或其对可移植器官的影响。然后，我们在异位心脏的小型模型中模拟了影响器官的环境因素。移植模型。我们发现，与非振动相比，中程振动会导致生存率降低心。移植的心脏显示细胞凋亡和肌动蛋白紊乱增加。还需要做更多的工作确定最合适的方式来护理运输途中的器官并降低运输过程中的潜在风险。该提案建立在我们在创新器官运输方面的专业知识的基础上。我们假设 CIT 是不仅仅是独处的时间，环境因素也可能影响移植物的存活。我们将分离压力、温度和振动，以了解每个因素如何单独影响移植器官更大的目标是实施减轻这些风险并改善器官功能的策略。在目标 1 中，我们将确定目前尚未测量的影响心脏的实际环境因素。通过汽车、直升机、飞机和无人机进行运输。我们将计算温度、压力和振动，并且比较每种运输方式的遥测结果。然后，我们将评估装运前和装运后的活检改变细胞粘附分子（ICAM-1、VCAM-1）和细胞骨架肌动蛋白。在目标 2 中，我们将对这些进行建模心脏移植动物模型中的力。供体心脏将经过压力、温度或振动。主要结果指标是移植物存活率。次要结果指标将是非如目标 1 所示，对粘附分子和肌动蛋白进行侵入性经胸超声心动图和组织学检查。在这里，我们将第一次了解到环境如何影响人体数千个器官在运输过程中。然后我们将了解多变量冷缺血时间的每个组成部分如何影响器官功能、免疫反应和移植物存活。这些发现共同将启动器官领域下一个十年的坚持。