糖尿病性勃起功能障碍(DED)的核心发病机制为阴茎海绵窦内皮功能障碍，现有疗法效果不佳。我们己证明尿源干细胞(USC)可改善DED大鼠阴茎海绵窦内皮及勃起功能，但其作用机制及调控节点尚不清楚。有研究发现由干细胞外泌体中miRNAs介导的旁分泌可能是干细胞治疗的主要作用机理。预实验发现USC在体外可分泌含miRNAs的外泌体，将USC移植入DED大鼠阴茎内可恢复部分miRNAs的表达。据此我们提出“USC通过外泌体中的miRNAs调控修复DED大鼠阴茎海绵窦内皮功能而改善其勃起功能”的假设。本项目结合基因芯片与蛋白芯片、分子生物学等方法探讨USC所分泌外泌体中的miRNAs介导不同信号通路之间交叉串话的机理，旨在获得USC通过外泌体调控修复DED大鼠内皮功能及勃起功能的直接证据，将助于更深刻地理解USC治疗DED的作用机制与调控节点，为推动干细胞疗法成为勃起功能障碍治疗的新手段提供理论依据。

The core pathologic mechanism of diabetic erectile dysfunction (DED) is endothelial dysfunction. However, current treatment for DED is insufficient. Our previous studies demonstrated that urine derived stem cells (USCs) could significantly improve the penile cavernous endothelial function and erectile function of DED rats, but the pathway and key regulation point of USCs repair the endothelial dysfunction remain unclear. Some other studies showed that paracrine mechanism mediated by the exosomes enrich miRNAs which were secreted by stem cells was an important mechanism for the stem cell therapy. Our pilot study showed the USCs could secrete exosomes and these exosomes enrich miRNAs. The abnormal miRNAs in the penis of DED rats would be partly corrected by USCs transplantation. Therefore, we hypothesis that USCs can restore the impaired endothelial function and improve the erectile dysfunction of DED rats by the exosomes enrich miRNAs. We are planning to analyze the cross-talk mechanisms of different signaling pathway mediated by the miRNAs regulation network by gene microarray, RPPA analysis and bioinformatics prediction et al. This project is aim to obtain the direct evidence that USCs can restore the endothelial dysfunction and erectile dysfunction by secreting exosomes enrich miRNAs. It will contribute to a better understanding of the mechanisms and key regulation node of USCs in the treatment of erectile dysfunction, which may also provide a theoretical basis for promoting the stem cell therapy in the treatment of DED.