Protection of donor kidneys with synchronization modulation electric field (SMEF)

通过同步调制电场 (SMEF) 保护供肾

基本信息

批准号：
10384061
负责人：
WEI CHEN
金额：
$ 25.13万
依托单位：
WR BIOTECH, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-23 至 2022-09-18
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10384061
关键词：
Active Biological Transport Apoptosis Autologous Transplantation Body Temperature Cardiac Death Cell Volumes Cell membrane Clinical Trials Closure by clamp Consumption Creatinine Cryopreservation Development Devices End stage renal failure Equilibrium Exhibits Frequencies Graft Survival Half-Life Histology Hour Hypoxia Impairment Incidence Injury to Kidney Ions Ischemia Kidney Kidney Transplantation Legal patent Life Measures Medical Device Membrane Potentials Mus Na(+)-K(+)-Exchanging ATPase Names Necrosis Organ Organ Transplantation Patients Pattern Phase Physiologic pulse Physiological Plasma Prevention Procedures Pump Renal function Reperfusion Injury Risk Factors Saline Same-sex Savings Seminal Survival Rate Techniques Testing Transplantation Warm Ischemia base delayed graft function design electric field experience graft function improved ischemic injury novel novel strategies porcine model pre-clinical success transplant model

项目摘要

The objective of this proposal is to examine a novel technique called improved Synchronization Modulation Electric Field (i-SMEF) in protection of donor kidneys and improvement of transplanted graft functions. We will apply the i-SMEF on donor kidneys during cold storage and evaluate the transplanted graft function following kidney transplantation in mice. We have developed a novel technique, named i-SMEF, which could not only maintain the pump functions, but also generate ATP molecules. Briefly, on the one hand, i-SMEF maintains Na/K pump activity to actively transport three Na+ out and two K+ ions in by consuming one ATP molecule, on the other hand, the electric field provides energy to the pump molecules so that they can synthesize one ATP in each pumping cycle. Consequently, the ATP net-consumption for the i-SMEF-controlled Na/K pumps is theoretically zero at any pumping rate, in other words, the pump molecules can effectively build up physiological ionic concentration gradients in the situations with a limited or lack of ATP supply, such as in hypoxia. Based on the strong preliminary findings, we propose to test this technique in a mouse kidney transplantation model. We will test our hypothesis that application of the i-SMEF on donor kidneys during cold storage protects against ischemic injury and improves the transplanted graft functions.

该提案的目的是研究一种称为改进同步的新技术调制电场 (i-SMEF) 保护供肾并改善肾功能移植后的移植物功能。我们将在冷藏期间将 i-SMEF 应用于供体肾脏，并评估小鼠肾移植后移植肾的功能。我们开发了一种新技术，名为 i-SMEF，它不仅可以维护泵功能，而且还产生 ATP 分子。简而言之，一方面，i-SMEF 维持 Na/K 通过消耗 1 个 ATP 主动输送 3 个 Na+ 离子和 2 个 K+ 离子输入的泵活性另一方面，电场为泵分子提供能量，使它们在每个泵循环中可以合成一个ATP。因此，ATP 净消耗量为 i-SMEF 控制的 Na/K 泵理论上在任何泵送速率下均为零，换句话说，泵分子可以在以下情况下有效地建立生理离子浓度梯度 ATP 供应有限或缺乏，例如缺氧。基于强有力的初步研究结果，我们建议在小鼠肾脏中测试这项技术移植模型。我们将检验我们的假设，即 i-SMEF 在供体肾脏上的应用冷藏期间可防止缺血性损伤并改善移植物的功能。