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Exosome Released From Schwann Cells May Be Involved in Microenergy Acoustic Pulse–Associated Cavernous Nerve Regeneration
Institution:1. Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA;2. Department of Urology, Third Xiangya Hospital of Central South University, Changsha, China;3. Department of Urology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China;1. Institute for Family and Sexuality Studies, Department of Neurosciences, University of Leuven, Leuven, Belgium;2. Kinsey Institute, Indiana University, IN, USA;3. Liberos, Los Angeles, CA, USA;4. The Schiefelbusch Institute for Life Span Studies, University of Kansas, Lawrence, KS, USA;5. Department of Psychiatry, University of Wisconsin, Madison, WI, USA;6. Department of Psychology, University of Minnesota, Minneapolis, MN, USA;7. Department of Family Medicine and Community Health, University of Minnesota, Minneapolis, MN, USA;1. Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China;2. Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China;3. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, China;4. Key Laboratory of Population Health Across Life Cycle, Anhui Medical University, Hefei, China;5. Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China;1. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;2. Department of Urology, Affiliated Hospital of Nantong University, Nantong, China;3. Department of Urology, The Affiliated Kizilsu Kirghiz Autonomous Prefecture People''s Hospital of Nanjing Medical University, Artux, China;1. Division of Urology, Urologic Reconstruction, Urodynamics, and Female Urology, Department of Surgery, Cedars-Sinai Medical Center, Beverly Hills, CA, USA;2. Stanford University School of Medicine, Stanford, CA, USA;3. Division of Dermatology, Albert Einstein College of Medicine, The Bronx, NY, USA;4. University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA;1. Department of Urology, Seoul National University Boramae Medical Center, Seoul, Korea;2. Department of Urology, Seoul National University College of Medicine, Seoul, Korea;1. Department of Spine Surgery, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha 410011, Hunan, China;2. Department of Orthopaedic Surgery, Stanford University, 300 Pasteur Dr, Stanford, CA 94305, USA
Abstract:BackgroundNeurogenic 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.AimTo establish a new model in vitro to simulate nerve injury in neurogenic ED and to explore the mechanisms of MAP in vitro.MethodsSprague-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/mm2, 1 Hz, 100 pulses), and SC exosomes were isolated. The MPG and CN/MPG were treated with MAP (0.033 mJ/mm2, 1 Hz) at different dosages (25, 50, 100, 200, or 300 pulses) or exosomes derived from MAP-treated SCs in vitro.OutcomesNeurite 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.ResultsNeurite 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.Clinical ImplicationsMAP may have utility in the treatment of neurogenic ED by SC-derived exosomes.Strength & LimitationsWe 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.ConclusionThis 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.
Keywords:Microenergy Acoustic Pulse  Schwann Cells  Exosome  Major Pelvic Ganglion  Nerve Regeneration
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