Exosomes derived from mesenchymal stem cells exert therapeutic effect in a rat model of cavernous nerves injury
Exosomes derived from mesenchymal stem cells exert therapeutic effect in a rat model of cavernous nerves injury
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源自间充质干细胞的外泌体在大鼠海绵体神经损伤模型中发挥治疗作用。
DOI：
10.1111/andr.12519
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发表时间：
2018-11-01
期刊：
影响因子：
4.5
通讯作者：
Guan, R.
中科院分区：
文献类型：
--
作者：
Li, M.;Lei, H.;Guan, R.
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。至今仍缺乏有效的治疗方法。本研究将48只成年雄性SD大鼠随机分为4组，每组10只，分别为假手术组、双侧海绵体神经损伤组、脂肪间充质干细胞exosomes组组4-BCNI+骨髓来源的间充质干细胞（BMSC）来源的外泌体（BMSC-Exo）。手术后21天，在组织采集前测量勃起功能。然后进行组织学和Western印迹分析。外泌体能够在体外内化到人脐静脉内皮细胞（HUVEC）中，并且可以在体内阴茎海绵体中检测到。BCNI组大鼠阴茎背神经（DN）和盆大神经节（MPG）的nNOS表达、DN神经丝蛋白水平、血管内皮标志物vWF、α-平滑肌肌动蛋白（α-SMA）、平滑肌与胶原含量的比值均明显低于Sham组，ADSC-Exo和BMSC-Exo组上述组织病理学改变明显恢复。此外，与BCNI组相比，ADSC-Exo或BMSC-Exo治疗的BCNI组的平均海绵体内压/平均动脉压比值显著升高。结果表明，ADSC-Exo和BMSC-Exo治疗均可明显减轻BCNI相关大鼠的病理改变，改善其勃起功能。来源于ADSC和BMSCs的Exosomes可能是pRP-ED治疗的潜在药物。
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 (alpha-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.