Molecular Biology Laboratory of Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Andrology. 2018 Nov;6(6):927-935. doi: 10.1111/andr.12519. Epub 2018 Jul 16.
Postradical prostatectomy erectile dysfunction (pRP-ED) is a major health issue. There has been a shortage of an effective treatment method until now. In this study, a total of 48 adult male Sprague-Dawley (SD) rats were randomly equally divided into four groups, including group 1-sham surgery with cavernous nerve exposure plus vehicle, group 2-bilateral cavernous nerve injury (BCNI) plus vehicle, group 3-BCNI plus adipose-derived mesenchymal stem cells (ADSCs)-derived exosomes (ADSC-Exo), and group 4-BCNI plus bone marrow-derived mesenchymal stem cell (BMSCs)-derived exosomes (BMSC-Exo). Twenty-one days following surgery, erectile function was measured before tissue harvest. Histologic and Western blot analyses were then performed. Exosomes were capable of internalization into human umbilical vein endothelial cells (HUVEC) in vitro and could be detected in the corpus cavernosum in vivo. The nNOS expression in the penile dorsal nerves (DN) and major pelvic ganglion (MPG), protein level of neurofilament in the DN, endothelial markers vWF, alpha smooth muscle actin (α-SMA), the ratio of smooth muscle to collagen content were obviously lower in BCNI group compared with the sham group, while ADSC-Exo and BMSC-Exo groups resulted in significant restoration of the above histopathological changes. Moreover, BCNI treated with ADSC-Exo or BMSC-Exo had significantly higher mean intracavernous pressure/mean arterial pressure ratio compared with BCNI group. The results demonstrated that both ADSC-Exo and BMSC-Exo treatment could significantly alleviate pathological changes and improve the erectile function in BCNI-related rats. Exosomes derived from ADSCs and BMSCs may be a potential agent for pRP-ED treatment.
根治性前列腺切除术后勃起功能障碍(pRP-ED)是一个主要的健康问题。到目前为止,还没有有效的治疗方法。在这项研究中,共将 48 只成年雄性 Sprague-Dawley(SD)大鼠随机平均分为四组,包括:1 组-假手术伴海绵体神经暴露加载体、2 组-双侧海绵体神经损伤(BCNI)加载体、3 组-BCNI 加脂肪间充质干细胞(ADSCs)衍生的外泌体(ADSC-Exo)和 4 组-BCNI 加骨髓间充质干细胞(BMSCs)衍生的外泌体(BMSC-Exo)。术后 21 天,在组织采集前测量勃起功能。然后进行组织学和 Western blot 分析。外泌体能够在体外被人脐静脉内皮细胞(HUVEC)内化,并能在体内被检测到海绵体中。阴茎背神经(DN)和主要骨盆神经节(MPG)中的 nNOS 表达、DN 中的神经丝蛋白水平、内皮标志物 vWF、α平滑肌肌动蛋白(α-SMA)、平滑肌与胶原含量的比值在 BCNI 组明显低于假手术组,而 ADSC-Exo 和 BMSC-Exo 组则明显恢复了上述组织病理学变化。此外,与 BCNI 组相比,BCNI 经 ADSC-Exo 或 BMSC-Exo 处理后,海绵体内压/平均动脉压比值显著升高。结果表明,ADSC-Exo 和 BMSC-Exo 治疗均可显著减轻 BCNI 相关大鼠的病理变化,改善勃起功能。ADSCs 和 BMSCs 衍生的外泌体可能是治疗 pRP-ED 的一种潜在药物。