Transplantation of Human Urine-Derived Stem Cells Transfected with Pigment Epithelium-Derived Factor to Protect Erectile Function in a Rat Model of Cavernous Nerve Injury
Transplantation of Human Urine-Derived Stem Cells Transfected with Pigment Epithelium-Derived Factor to Protect Erectile Function in a Rat Model of Cavernous Nerve Injury
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DOI：
10.3727/096368916x691448
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发表时间：
2016-11
影响因子：
3.3
通讯作者：
Qiyun Yang;Xin Chen;Tao Zheng;Dayu Han;Heng Zhang;Yanan Shi;J. Bian;Xiangzhou Sun;Kai Xia
中科院分区：
文献类型：
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作者：
Qiyun Yang;Xin Chen;Tao Zheng;Dayu Han;Heng Zhang;Yanan Shi;J. Bian;Xiangzhou Sun;Kai Xia
本研究旨在探讨海绵体内注射尿源性干细胞(USCs)或经色素上皮衍生因子(PEDF)基因修饰的USCs对双侧海绵体神经损伤所致勃起功能障碍(CNIED)大鼠勃起功能和海绵体结构的保护作用。USCs取自6名健康男性捐献者的尿液。75只大鼠随机分为假手术组、双侧海绵体神经挤压伤(BCNI)组、USC组、USCGFP+组和USCGFP/PEDF+组，每组15只。假手术组仅行无CN挤压伤的剖腹手术加海绵体内注射磷酸盐缓冲液(PBS)。其余各组分别行BCNI和海绵体内注射PBS、USCs、USCsGFP+或USCsGFP/PEDF+。记录海绵体内总压(ICP值)及ICPMAP比值(ICPMAP)。在阴茎组织内对阴茎背神经、内皮和平滑肌进行了评估。细胞移植28d后，USC组和USCGFP/PEDF+组的ICP值和ICPMAP比值均显著升高(p<；0.05)。免疫组织化学和Western印迹分析表明，USCsGFP/PEDF+对勃起功能和海绵体结构的保护作用与阴茎背神经内神经元型一氧化氮合酶阳性纤维的数量增加、内皮标志物(CD31和eNOS)和平滑肌标志物(平滑蛋白)的表达增加、平滑肌与胶原的比率增加、转化生长因子-β1(TGFR-β1)的表达减少以及海绵体组织中的细胞凋亡有关。USCs和USCsGFP/PEDF+的旁分泌作用通过神经保护防止CNIED模型大鼠勃起功能和海绵体结构的破坏，从而改善内皮细胞功能，增加海绵体组织中的平滑肌含量，减少海绵体组织的纤维化和细胞凋亡。
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 six healthy male donors. Seventy-five rats were randomly divided into five groups (n = 15 per group): sham, bilateral cavernous nerve (CN) crush injury (BCNI), USC, USCGFP+, and USCGFP/PEDF+ groups. The sham group received only laparotomy without CN crush injury and intracavernous injection with phosphate-buffered saline (PBS). All of the other groups were subjected to BCNI and intracavernous injection with PBS, USCs, USCsGFP+, or USCsGFP/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 USCGFP/PEDF+ groups displayed more significantly enhanced ICP and ICP/MAP ratio (p < 0.05) 28 days after cell transplantation. Immunohistochemistry (IHC) and Western blot analysis demonstrated that the protection of erectile function and the cavernous structure by USCsGFP/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 (TGF-β1), and decreased cell apoptosis in the cavernous tissue. The paracrine effect of USCs and USCsGFP/PEDF+ prevented the destruction of erectile function and the cavernous structure in the CNIED rat model by nerve protection, thereby improving endothelial cell function, increasing the smooth muscle content, and decreasing fibrosis and cell apoptosis in the cavernous tissue.