Embryonic stem cell-derived extracellular vesicle-mimetic nanovesicles rescue erectile function by enhancing penile neurovascular regeneration in the streptozotocin-induced diabetic mouse.
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| 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 μm). Here, we demonstrate in diabetic mice that embryonic stem cell (ESC)-derived EV-mimetic NVs (ESC-NVs) completely restore erectile function (~96% of control values) through enhanced penile angiogenesis and neural regeneration in vivo, whereas ESC partially restores erectile function (~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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| Authors | Mi-Hye Kwon, Kang-Moon Song, Anita Limanjaya, Min-Ji Choi, Kalyan Ghatak, Nhat Minh Nguyen, Jiyeon Ock, Guo Nan Yin, Ju-Hee Kang, Man Ryul Lee, Yong Song Gho, Ji-Kan Ryu, Jun-Kyu Suh |
| Journal | Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 20072 (12 27 2019) ISSN: 2045-2322 [Electronic] England |
| PMID | 31882614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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