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

通过同步调制电场 (SMEF) 保护供肾

• 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
• 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

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.

本提案的目的是研究一种称为改进同步的新技术