Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA; Department of Urology, Third Xiangya Hospital of Central South University, Changsha, China.
Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.
J Sex Med. 2020 Sep;17(9):1618-1628. doi: 10.1016/j.jsxm.2020.05.018. Epub 2020 Jul 12.
Neurogenic erectile dysfunction (ED) is often refractory to treatment because of insufficient functional nerve recovery after injury or insult. Noninvasive mechano-biological intervention, such as microenergy acoustic pulse (MAP), low-intensity pulsed ultrasound, and low-intensity extracorporeal shockwave treatment, is an optimal approach to stimulate nerve regeneration.
To establish a new model in vitro to simulate nerve injury in neurogenic ED and to explore the mechanisms of MAP in vitro.
Sprague-Dawley rats were used to isolate Schwann cells (SCs), major pelvic ganglion (MPG), and cavernous nerve with MPG (CN/MPG). SCs were then treated with MAP (0.033 mJ/mm, 1 Hz, 100 pulses), and SC exosomes were isolated. The MPG and CN/MPG were treated with MAP (0.033 mJ/mm, 1 Hz) at different dosages (25, 50, 100, 200, or 300 pulses) or exosomes derived from MAP-treated SCs in vitro.
Neurite growth from the MPG fragments and CN was photographed and measured. Expression of neurotropic factors (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) was checked.
Neurite outgrowth from MPG and CN/MPG was enhanced by MAP in a dosage response manner, peaking at 100 pulses. MAP promoted SC proliferation, neurotropic factor (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3) expression, and exosome secretion. SC-derived exosomes significantly enhanced neurite outgrowth from MPG in vitro.
MAP may have utility in the treatment of neurogenic ED by SC-derived exosomes.
STRENGTH & LIMITATIONS: We confirmed that MAP enhances penile nerve regeneration through exsomes. Limitations of this study include that our study did not explore the exact mechanisms of how MAP increases SC exosome secretion nor whether MAP modulates the content of exosomes.
This study revealed that neurite outgrowth from MPG was enhanced by MAP and by SC-derived exosomes which were isolated after MAP treatment. Our findings indicate that one mechanism by which MAP induces nerve regeneration is by stimulation of SCs to secrete exosomes. Peng D, Reed-Maldonado AB, Zhou F, et al. Exosome Released From Schwann Cells May Be Involved in Microenergy Acoustic Pulse-Associated Cavernous Nerve Regeneration. J Sex Med 2020;17:1618-1628.
神经源性勃起功能障碍（ED）通常对治疗反应不佳，因为损伤或损伤后功能性神经恢复不足。非侵入性机械生物学干预，如微能量声脉冲（MAP）、低强度脉冲超声和低强度体外冲击波治疗，是刺激神经再生的最佳方法。
建立一种新的体外模型来模拟神经源性 ED 中的神经损伤，并探讨 MAP 的体外机制。
使用 Sprague-Dawley 大鼠分离雪旺细胞（SCs）、主要骨盆神经节（MPG）和伴有 MPG 的海绵体神经（CN/MPG）。然后用 MAP（0.033 mJ/mm，1 Hz，100 个脉冲）处理 SCs，并分离 SC 外泌体。用 MAP（0.033 mJ/mm，1 Hz）以不同剂量（25、50、100、200 或 300 个脉冲）或 MAP 处理的 SC 衍生的外泌体处理 MPG 和 CN/MPG。
用 MAP 以剂量反应方式增强 MPG 片段和 CN 的神经突生长，在 100 个脉冲时达到峰值。MAP 促进了 SC 的增殖、神经营养因子（脑源性神经营养因子、神经生长因子和神经营养因子-3）的表达和外泌体的分泌。SC 衍生的外泌体显著增强了 MPG 的体外神经突生长。
MAP 通过 SC 衍生的外泌体可能对治疗神经源性 ED 具有实用性。
我们证实 MAP 通过外泌体增强阴茎神经再生。本研究的局限性包括，我们的研究没有探索 MAP 增加 SC 外泌体分泌的确切机制，也没有探讨 MAP 是否调节外泌体的含量。
这项研究表明，MAP 增强了 MPG 的神经突生长，并增强了 MAP 处理后分离的 SC 衍生的外泌体。我们的研究结果表明，MAP 诱导神经再生的一种机制是通过刺激 SC 分泌外泌体。Peng D、Reed-Maldonado AB、Zhou F 等。雪旺细胞释放的外泌体可能参与微能量声脉冲相关海绵体神经再生。J Sex Med 2020；17：1618-1628。
