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.

该二期应用的目标：1）确定i-SMEF（改进的 使用成年约克夏肾猪的临床前动物模型中的同步调制电场） 自体移植； 2) 确定 i-SMEF 预防缺血性损伤的最佳参数 供体肾脏在冷藏期间的状态和移植肾功能的改善。 在第一阶段提案中，我们开发了一种新技术，名为 i-SMEF（正在申请专利）。 i-SMEF 不仅控制Na/K泵活性，而且还产生ATP分子。简而言之，通过利用内在的对偶 Na/K泵的能量转换功能，我们专门设计了i-SMEF来控制Na/K泵的活动。 同时，电场为泵浦分子提供足够的能量，使其能够合成一种 每个泵循环的 ATP 分子。因此，i-SMEF 可以维持 Na/K 泵送活性 ATP 供应不足或缺乏的情况，例如缺氧。然后，我们证明了 i-SMEF在供肾上的应用有效保护了小鼠的移植肾功能 肾移植模型。这些数据刚刚发表在《科学转化医学》杂志上。 在此第二阶段提案中，我们将通过使用临床前研究来检验 i-SMEF 的转化意义 成年约克夏猪的猪模型。最大限度地减少免疫反应并关注缺血再灌注 损伤后，我们将采用自体肾移植模型。然后，我们将确定最佳参数，包括 电极对的数量、频率和电压。考虑到尺寸、解剖结构和结构的高度相似性 人类和成年猪肾脏的生理学之间的关系，我们认为从猪身上获得的最佳参数 在第三阶段提案中很容易适用于人类。