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: 10603207
• 负责人: WEI CHEN
• 金额: $ 80.33万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603207
• 关键词: Adult; Anatomy; Animal Model; Autologous Transplantation; Back; Clinical Trials; Creatinine; Cryopreservation; Data; Devices; Electrodes; Equipment; Family suidae; Flushing; Frequencies; Funding; General Hospitals; Goals; Histology; Hour; Human; Hypoxia; Immune response; Injury; Injury to Kidney; Investments; Kidney; Kidney Transplantation; LCN2 gene; Legal patent; Measures; Medical Device; Mitochondria; Modeling; Multi-Institutional Clinical Trial; Mus; Names; Nephrectomy; Phase; Physiology; Plasma; Production; Publishing; Pump; Renal function; Reperfusion Injury; Secure; Seminal; Techniques; Testing; Tissues; Translational Research; Transplantation; Universities; Urine; Wisconsin; base; cell type; design; electric field; graft function; improved; ischemic injury; kidney biopsy; novel; porcine model; pre-clinical; preservation; success; translational medicine; transplant model; voltage

The goals of this Phase II application: 1) determine the translational significance of the i-SMEF (improved Synchronization Modulation Electric Field) in a preclinical animal model using adult Yorkshire pigs with kidney autotransplantation; and 2) determine the optimal parameters of the i-SMEF in protection against ischemic injury of the donor kidneys during cold storage and improvement of the transplanted graft function. In the Phase I proposal, we have developed a novel technique, named i-SMEF (patent pending). The i-SMEF not only controls the Na/K pump activity, but also generates ATP molecules. Briefly, by utilizing the intrinsic dual energy transform functions of the Na/K pumps, we specially designed the i-SMEF to control Na/K pump activity. Meanwhile, the electric field provides adequate energy to the pump molecules so that they can synthesize one ATP molecule for each pumping cycle. Consequently, the i-SMEF can maintain the Na/K pumping activity in situations with an insufficient or lack of ATP supply, such as in hypoxia. Then, we demonstrated that the application of the i-SMEF on the donor kidneys effectively protected transplanted graft functions in a mouse kidney transplantation model. These data have just been published in Science Translational Medicine. In this Phase II proposal, we will examine the translational significance of the i-SMEF by using a preclinical porcine model in adult Yorkshire pigs. To minimize the immunoresponse and focus on the ischemia reperfusion injury, we will use kidney autotransplantation model. Then, we will determine the optimal parameters, including the numbers of electrode pairs, frequency, and voltage. Considering the high similarities in size, anatomy and physiology between human and adult pig kidneys, we believe that the optimal parameters obtained from pigs are readily applicable to humans in the Phase III proposal.

该阶段应用程序的目标：1）确定I-Smef的翻译意义（改进了 使用肾脏的成人约克郡猪在临床前动物模型中的同步调制电场） 自动移植； 2）确定I-SMEF的最佳参数，以防止缺血性损伤 在冷藏和改善移植移植功能的过程中供体肾脏的肾脏。 在第一阶段的建议中，我们开发了一种新型技术，名为I-Smef（专利申请）。 i-smef 不仅控制Na/K泵活性，而且还会产生ATP分子。简而言之，利用固有的双重 Na/k泵的能量转换功能，我们专门设计了I-SMEF来控制Na/K泵活动。 同时，电场为泵分子提供足够的能量，以便它们可以合成一个 每个泵送周期的ATP分子。因此，i-Smef可以维持Na/k的泵送活动 不足或缺乏ATP供应的情况，例如缺氧。然后，我们证明了 I-SMEF在供体肾脏上的应用有效地保护了小鼠的移植移植功能 肾移植模型。这些数据刚刚发表在《科学转化医学》上。 在此II阶段提案中，我们将通过使用临床前检查I-SMEF的翻译意义 成人约克郡猪的猪模型。最大程度地减少免疫响应并专注于缺血再灌注 受伤，我们将使用肾脏自动移植模型。然后，我们将确定最佳参数，包括 电极对，频率和电压的数量。考虑大小，解剖学和 人类和成人猪肾之间的生理学，我们认为从猪获得的最佳参数 在第三阶段提案中很容易适用于人类。