Embryonic stem cell-derived extracellular vesicle-mimetic nanovesicles rescue erectile function by enhancing penile neurovascular regeneration in the streptozotocin-induced diabetic mouseopen access
- Authors
- Kwon, Mi-Hye; Song, Kang-Moon; Limanjaya, Anita; Choi, Min-Ji; Ghatak, Kalyan; Nhat Minh Nguyen; Ock, Jiyeon; Yin, Guo Nan; Kang, Ju-Hee; Lee, Man Ryul; Gho, Yong Song; Ryu, Ji-Kan; Suh, Jun-Kyu
- Issue Date
- 27-Dec-2019
- Publisher
- Nature Publishing Group
- Keywords
- embryonic stem cell; exosome
- Citation
- Scientific Reports, v.9
- Journal Title
- Scientific Reports
- Volume
- 9
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/3738
- DOI
- 10.1038/s41598-019-54431-4
- ISSN
- 2045-2322
- Abstract
- Extracellular vesicles (EVs) have attracted particular interest in various fields of biology and medicine. However, one of the major hurdles in the clinical application of EV-based therapy is their low production yield. We recently developed cell-derived EV-mimetic nanovesicles (NVs) by extruding cells serially through filters with diminishing pore sizes (10, 5, and 1 mu m). Here, we demonstrate in diabetic mice that embryonic stem cell (ESC)-derived EV-mimetic NVs (ESC-NVs) completely restore erectile function (similar to 96% of control values) through enhanced penile angiogenesis and neural regeneration in vivo, whereas ESC partially restores erectile function (similar to 77% of control values). ESC-NVs promoted tube formation in primary cultured mouse cavernous endothelial cells and pericytes under high-glucose condition in vitro; and accelerated microvascular and neurite sprouting from aortic ring and major pelvic ganglion under high-glucose condition ex vivo, respectively. ESC-NVs enhanced the expression of angiogenic and neurotrophic factors (hepatocyte growth factor, angiopoietin-1, nerve growth factor, and neurotrophin-3), and activated cell survival and proliferative factors (Akt and ERK). Therefore, it will be a better strategy to use ESC-NVs than ESCs in patients with erectile dysfunction refractory to pharmacotherapy, although it remains to be solved for future clinical application of ESC.
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Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
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