The aim of this study was to investigate whether intracavernous injection of urine-derived stem cells (USCs) or USCs genetically modified with pigment epithelium-derived factor (PEDF) could protect the erectile function and cavernous structure in a bilateral cavernous nerve injury-induced erectile dysfunction (CNIED) rat model.
USCs were cultured from the urine of 6 healthy male donors. Seventy-five rats were randomly divided into five groups (n=15 per group): Sham, BCNI, USC, USC(GFP+) and USC(GFP/PEDF+) group. Sham group received only laparotomy without cavernous nerve (CN) crushing injury and intracavernous injection with phosphate buffered saline (PBS). Other groups all received bilateral CN crushing injury (BCNI) and intracavernous injection with PBS, USCs, USCs(GFP+) or USCs(GFP/PEDF+), respectively. The total intracavernous pressure (ICP) and the ratio of ICP to mean arterial pressure (ICP/MAP) were recorded. The penile dorsal nerves, the endothelium and the smooth muscle were assessed within the penile tissue. The USC and USC(GFP/PEDF+) groups displayed more significantly enhanced ICP and ICP/MAP ratio (P<0.05) 28 days after cell transplantation. Immunohistochemistry and western blotting analysis demonstrated that the protection of erectile function and the cavernous structure by USC(GFP/PEDF+) was associated with an increased number of nNOS-positive fibers within the penile dorsal nerves, improved expression of endothelial markers (CD31 and eNOS) and a smooth muscle marker (Smoothelin), an enhanced smooth muscle to collagen ratio, decreased expression of transforming growth factor-β1 and decreased cell apoptosis in the cavernous tissue. The paracrine effect of USCs and USCs(GFP/PEDF+) prevented the destruction of erectile function and the cavernous structure in the CNIED rat model by nerve protection, thereby improving the endothelial function, increasing the smooth muscle content and decreasing fibrosis and cell apoptosis in the cavernous tissue.
Cell transplantation. 2016 Apr 08 [Epub ahead of print]
Qiyun Yang, Xin Chen, Tao Zheng, Dayu Han, Heng Zhang, Yanan Shi, Jun Bian, Xiangzhou Sun, Kai Xia, Xiaoyan Liang, Guihua Liu, Yuanyuan Zhang, Chunhua Deng