Pericyte-Derived Extracellular Vesicle-Mimetic Nanovesicles Restore Erectile Function by Enhancing Neurovascular Regeneration in a Mouse Model of Cavernous Nerve Injury
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SCOPUS
- Title
- Pericyte-Derived Extracellular Vesicle-Mimetic Nanovesicles Restore Erectile Function by Enhancing Neurovascular Regeneration in a Mouse Model of Cavernous Nerve Injury
- Authors
- Yin, G.N.; Park, S.-H.; Ock, J.; Choi, M.-J.; Limanjaya, A.; Ghatak, K.; Song, K.-M.; Kwon, M.-H.; Kim, D.-K.; Gho, Y.S.; Suh, J.-K.; Ryu, J.-K.
- Date Issued
- 2020-08
- Publisher
- ELSEVIER SCI LTD
- Abstract
- Background: Extracellular vesicle (EV)-mimetic nanovesicles (NVs) from embryonic stem cells have been observed to stimulate neurovascular regeneration in the streptozotocin-induced diabetic mouse. Pericytes play important roles in maintaining penile erection, yet no previous studies have explored the effects of pericyte-derived NVs (PC-NVs) in neurovascular regeneration in the context of erectile dysfunction. Aim: To investigate the potential effect of PC-NVs in neurovascular regeneration. Methods: PC-NVs were isolated from mouse cavernous pericytes, and neurovascular regeneration was evaluated in an in vitro study. Twelve-week-old C57BL/6J mice were used to prepare cavernous nerve injury model. Erectile function evaluation, histologic examination of the penis, and Western blots were assessed 2 weeks after model creation and PC-NVs treatment. Outcomes: The main outcomes of this study are PC-NVs characterization, intracavernous pressure, neurovascular regeneration in the penis, and in vitro functional evaluation. Results: The PC-NVs were extracted and characterized by cryotransmission electron microscopy and EV-positive (Alix, TSG101, CD81) and EV-negative (GM130) markers. In the in vivo studies, PC-NVs successfully improved erectile function in cavernous nerve injury mice (w82% of control values). Immunofluorescence staining showed significant increases in pericytes, endothelial cell, and neuronal contents. In the in vitro studies, PC-NVs significantly increased mouse cavernous endothelial cells tube formation, Schwann cell migration, and dorsal root ganglion and major pelvic ganglion neurite sprouting. Finally, Western blot analysis revealed that PC-NVs upregulated cell survival signaling (Akt and eNOS) and induced the expression of neurotrophic factors (brain-derived neurotrophic factor, neurotrophin-3, and nerve growth factor). Clinical Implications: PC-NVs may be used as a strategy to treat erectile dysfunction after radical prostatectomy or in men with neurovascular diseases. Strengths & Limitations: We evaluated the effect of PC-NVs in vitro and in a mouse nerve injury model, cavernous nerve injury. Additional studies are necessary to determine the detailed mechanisms of neurovascular improvement. Further study is needed to test whether PC-NVs are also effective when given weeks or months after nerve injury. Conclusion: PC-NVs significantly improved erectile function by enhancing neurovascular regeneration. Local treatment with PC-NVs may represent a promising therapeutic strategy for the treatment of neurovascular diseases. Copyright (C) 2020, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.
- Keywords
- PROSTATECTOMY IMPROVES RECOVERY; RADICAL PROSTATECTOMY; CORPUS CAVERNOSUM; DYSFUNCTION; DIFFERENTIATION; EXOSOMES; CELLS; REHABILITATION; MANAGEMENT; SECRETION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/104545
- DOI
- 10.1016/j.jsxm.2020.07.083
- ISSN
- 1743-6095
- Article Type
- Article
- Citation
- JOURNAL OF SEXUAL MEDICINE, vol. 17, no. 11, page. 2118 - 2128, 2020-08
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