Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
Life Sci. 2018 Aug 15;207:272-283. doi: 10.1016/j.lfs.2018.06.017. Epub 2018 Jun 18.
To investigate the effect of intracavernous injection of human umbilical cord blood derived endothelial colony forming cells (HUCB ECFCs) on erectile dysfunction (ED) in Zucker Diabetic Fatty (ZDF) rat model.
Erectile function was assessed by cavernous nerve electrostimulation in ZDF rats aged 20-28 weeks. Following confirmation of severe ED at the age of 28 weeks, 21 ZDF rats were randomly assigned to three experimental groups: 1 million ECFCs, 2 million ECFCs, and phosphate buffered saline (PBS). Four weeks after intracavernous injection, the efficacy of ECFCs was quantified by intracavernous pressure (ICP) measurement, Masson's trichrome staining, immunohistologic and immunoblot analyses and TUNEL assay.
Intracavernous ECFC administration improved ICP in a dose-dependent manner in comparison to the age-matched PBS group. Functional improvement in ICP was accompanied by a significant restoration of the cavernosal endothelial and smooth muscle cell content and cavernosal nerve function. The percentage eNOS and nNOS positive cavernosal cells, and their respective protein expression levels and nNOS positive cells in the dorsal penile nerve in 2 million ECFCs treated groups were significantly higher than the PBS group. TUNEL stain quantification showed a significant decrease in cavernosal apoptosis following ECFC treatment.
The results are expected to provide a scientific basis to further study the clinical application of HUCB ECFCs in ameliorating ED in human.
HUCB ECFCs significantly improved severe ED in ZDF rats through improvement of the nerve and endothelium function and restoration of smooth muscle in the cavernosum by overcoming the cavernosal apoptosis.
探讨人脐带来源的内皮祖细胞(HUCB ECFCs)经海绵体神经内注射对 Zucker 糖尿病肥胖(ZDF)大鼠勃起功能障碍(ED)的影响。
通过电刺激海绵体神经评估 20-28 周龄 ZDF 大鼠的勃起功能。28 周龄时确认严重 ED 后,将 21 只 ZDF 大鼠随机分为三组:100 万 ECFC 组、200 万 ECFC 组和磷酸盐缓冲液(PBS)组。经海绵体神经内注射 4 周后,通过测量海绵体压(ICP)、Masson 三色染色、免疫组织化学和免疫印迹分析以及 TUNEL 检测评估 ECFC 的疗效。
与同龄 PBS 组相比,经海绵体神经内注射 ECFC 可剂量依赖性地改善 ICP。ICP 的功能改善伴随着海绵体内皮和平滑肌细胞含量以及海绵体神经功能的显著恢复。200 万 ECFC 治疗组的 eNOS 和 nNOS 阳性海绵体细胞百分比及其各自的蛋白表达水平和背侧阴茎神经中的 nNOS 阳性细胞均明显高于 PBS 组。TUNEL 染色定量显示,经 ECFC 治疗后,海绵体凋亡明显减少。
这些结果有望为进一步研究 HUCB ECFCs 在改善人类 ED 中的临床应用提供科学依据。
HUCB ECFCs 通过克服海绵体凋亡,改善神经和内皮功能以及恢复海绵体平滑肌,显著改善 ZDF 大鼠的严重 ED。