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

第二阶段申请的目标是：1）确定i-SMEF（改进的 同步调制电场）在使用具有肾脏的成年约克郡猪的临床前动物模型中的作用 自体移植; 2）确定i-SMEF对缺血性损伤保护的最佳参数 供肾在冷藏期间的存活率和移植肾功能的改善。 在第一阶段的提案中，我们开发了一种新的技术，命名为i-SMEF（专利申请中）。i-SMEF 不仅控制Na/K泵的活性，还产生ATP分子。简单地说，通过利用内在对偶 利用Na/K泵的能量转换功能，我们专门设计了i-SMEF来控制Na/K泵的活性。 同时，电场为泵浦分子提供足够的能量，使它们能够合成一个 每个泵送周期的ATP分子。因此，i-SMEF可以维持Na/K泵活性， ATP供应不足或缺乏的情况，如缺氧。然后，我们证明， i-SMEF应用于供体肾有效地保护了小鼠中移植的移植物功能 肾移植模型这些数据刚刚发表在Science Translational Medicine上。 在这个II期计划中，我们将通过使用临床前实验来研究i-SMEF的转化意义。 成年约克郡猪的猪模型。减少免疫反应，关注缺血再灌注 损伤后，采用自体肾移植模型。然后，我们将确定最佳参数，包括 电极对数、频率和电压。考虑到它们在大小、解剖结构和 人和成年猪肾脏之间的生理学，我们认为，从猪获得的最佳参数 在第三阶段的提案中很容易适用于人类。

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.