Back to Search
Start Over
Pericyte-Derived Extracellular Vesicle–Mimetic Nanovesicles Restore Erectile Function by Enhancing Neurovascular Regeneration in a Mouse Model of Cavernous Nerve Injury
- Source :
- The Journal of Sexual Medicine. 17:2118-2128
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
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 (∼82% 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.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Urology
Endocrinology, Diabetes and Metabolism
030232 urology & nephrology
Extracellular Vesicles
Mice
03 medical and health sciences
0302 clinical medicine
Endocrinology
Erectile Dysfunction
Dorsal root ganglion
Neurotrophic factors
medicine
Animals
Humans
Regeneration
Tube formation
030219 obstetrics & reproductive medicine
business.industry
Penile Erection
Regeneration (biology)
Endothelial Cells
Extracellular vesicle
Nerve injury
Neurovascular bundle
Nerve Regeneration
Mice, Inbred C57BL
Disease Models, Animal
Psychiatry and Mental health
medicine.anatomical_structure
Reproductive Medicine
Pericyte
medicine.symptom
Pericytes
business
Penis
Subjects
Details
- ISSN :
- 17436109 and 17436095
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- The Journal of Sexual Medicine
- Accession number :
- edsair.doi.dedup.....a6b862e20659c887370c4c8d8825517d