尿源干细胞-PEDF基因联合水凝胶促进神经修复治疗海绵体神经损伤性勃起功能障碍及其机制

海绵体神经损伤性勃起功能障碍（CNIED）现有疗法效果不佳，促进海绵体神经（CN）修复是其治疗关键。我们研究发现尿源干细胞（USCs）可分泌能促进CN修复的色素上皮衍生因子（PEDF）；进一步研究发现USCs移植可部分改善CNIED大鼠的勃起功能，但遇到干细胞存活时间有限的瓶颈；我们另一研究发现水凝胶可改善USCs微环境、延长其存活时间。据此，我们提出通过USCs-PEDF基因联合水凝胶增强PEDF分泌、促进CN修复，进而治疗CNIED的科学设想。本项目拟应用水凝胶加载PEDF基因修饰的USCs治疗CNIED大鼠，采用分子生物学等方法，旨在获得USCs-PEDF基因联合水凝胶增强PEDF分泌、促进CN修复进而改善勃起功能的可靠证据，从激活NFκB信号通路诱导神经元细胞分泌多种抗凋亡因子和神经营养因子的角度阐明其机制；为USCs-PEDF基因联合水凝胶作为CNIED的新疗法提供充分科学依据。

The exist treatment for erectile dysfunction of cavernous nerve injury(CNIED) is not effective enough, and the key point is to promote cavernous nerve(CN) regeneration. Our study found that urine derived stem cells(USCs) can secrete pigment epithelial derived factor(PEDF) and promote CN regeneration. Further study demonstrated USCs transplantation can partially recover erectile function of CNIED rats, but the bottleneck of the USCs therapy is the limited survival time. Our study also confirmed the hyaluronan-heparin hydrogel was able to improve local microenvironment and prolong survival time of USCs. Therefore, we hypothesis that USCs-PEDF gene loaded in hyaluronan-heparin hydrogel can treat CNIED by increasing PEDF gene expression and promoting cavernous nerve regeneration. We are planning to transplant USCs modified PEDF gene combined with hyaluronan-heparin hydrogel in a CNIED rat model, found the reliable evidence of USCs-PEDF gene loaded in hyaluronan-heparin hydrogel to promote PEDF gene expression and nerve regeneration and then improve erectile function by using molecular biology techniques and other methods in vivo, evaluate the efficacy and safety of this therapy. This proposal aim to clarify the mechanism of PEDF promoting CN regeneration through activating NFκB pathway, and provide reliable scientific evidence for USCs-PEDF loaded in hyaluronan-heparin hydrogel as a new therapy for CNIED.