Chen Fengzhi, Zhang Haibo, Wang Zhiqiang, Ding Wei, Zeng Qinyu, Liu Wenbing, Huang Can, He Shuhua, Wei Anyang
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Urology, The First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine, Guiyang, China.
J Sex Med. 2017 Sep;14(9):1084-1094. doi: 10.1016/j.jsxm.2017.07.005. Epub 2017 Aug 7.
The efficacy of adipose-derived stem cells (ADSCs) in alleviating erectile dysfunction (ED) of diabetic rats has been demonstrated mainly through a paracrine effect. However, exosomes (EXOs), which are important bioactive substance vectors secreted by ADSCs, have never been associated with ED.
To investigate the effect of ADSC-derived EXOs on erectile function in a type 2 diabetic ED rat model.
EXOs were isolated from the supernatants of cultured ADSCs by ultracentrifugation. We constructed a type 2 diabetic rat model using a high-fat diet and low-dose streptozotocin administered by intraperitoneal injection. In total, 24 diabetic rats were randomly assigned to three groups and were treated with an intracavernous injection of ADSC-derived EXOs, ADSCs, or phosphate buffered saline. Another eight age-matched rats underwent sham operation and composed the normal control group.
Intracavernous pressure and mean arterial pressure testing and histologic and western blot analyses were performed 4 weeks after the intracavernous injection.
ADSC-derived EXOs and ADSCs administered by intracavernous injection led to an increase in the ratio of intracavernous pressure to mean arterial pressure compared with that for phosphate buffered saline treatment. Histologic and western blot analyses demonstrated an increased ratio of smooth muscle to collagen, increased expression of an endothelial marker (CD31), a smooth muscle marker (α-smooth muscle actin), and antiapoptotic protein Bcl-2 and decreased the expression of the apoptotic protein cleaved caspase-3 and apoptosis of endothelial and smooth muscle cells in the corpus cavernosum tissue after EXO or ADSC injection compared with values for the phosphate buffered saline treatment.
The present results are expected to provide a scientific foundation for clinical application in the near future.
Although the results demonstrated that intracavernous injection of ADSC-derived EXOs could ameliorate ED of diabetic rats, the optimum dose and times of injection remain for further study.
ADSC-derived EXOs, similarly to ADSCs, were capable of rescuing corpus cavernosum endothelial and smooth muscle cells by inhibiting apoptosis and thus promoting the recovery of erectile function in type 2 diabetic rats. Chen F, Zhang H, Wang Z, et al. Adipose-Derived Stem Cell-Derived Exosomes Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes. J Sex Med 2017;14:1084-1094.
脂肪来源干细胞（ADSCs）在改善糖尿病大鼠勃起功能障碍（ED）方面的疗效主要通过旁分泌作用得以证实。然而，作为ADSCs分泌的重要生物活性物质载体，外泌体（EXOs）从未被认为与ED有关。
探讨ADSC来源的EXOs对2型糖尿病性ED大鼠模型勃起功能的影响。
通过超速离心从培养的ADSCs上清液中分离EXOs。采用高脂饮食联合腹腔注射低剂量链脲佐菌素构建2型糖尿病大鼠模型。将24只糖尿病大鼠随机分为三组，分别给予海绵体内注射ADSC来源的EXOs、ADSCs或磷酸盐缓冲液。另外8只年龄匹配的大鼠接受假手术，组成正常对照组。
海绵体内注射4周后进行海绵体内压和平均动脉压检测以及组织学和蛋白质印迹分析。
与磷酸盐缓冲液治疗组相比，海绵体内注射ADSC来源的EXOs和ADSCs可使海绵体内压与平均动脉压的比值升高。组织学和蛋白质印迹分析表明，与磷酸盐缓冲液治疗组相比，EXO或ADSC注射后海绵体组织中平滑肌与胶原的比值增加，内皮标志物（CD31）、平滑肌标志物（α-平滑肌肌动蛋白）和抗凋亡蛋白Bcl-2的表达增加，凋亡蛋白裂解型半胱天冬酶-3的表达降低，内皮细胞和平滑肌细胞的凋亡减少。
本研究结果有望在不久的将来为临床应用提供科学依据。
尽管结果表明海绵体内注射ADSC来源的EXOs可改善糖尿病大鼠的ED，但最佳注射剂量和时间仍有待进一步研究。
ADSC来源 的EXOs与ADSCs相似，能够通过抑制细胞凋亡来挽救海绵体内皮细胞和平滑肌细胞，从而促进2型糖尿病大鼠勃起功能的恢复。陈F，张H，王Z等。脂肪来源干细胞衍生的外泌体改善2型糖尿病大鼠模型的勃起功能障碍。《性医学杂志》2017；14：1084 - 1094。
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