AB084. intracavernous administration of embryonic stem cell-derived exosome restores erectile function through penile neurovascular regeneration in the streptozotocin-induced diabetic mouse

BACKGROUND: Exosome contains a variety of protein, mRNA, and miRNA and is known to play an important role in intercellular communication as a bio-nanoparticle with a diameter of 40 to 100 nm. Recent studies have demonstrated the therapeutic potential of exosome in a variety of animal models for cardiovascular diseases and neuropathies. The aim of this study was to investigate effectiveness of embryonic stem cell (ESC)-derived exosome in restoring erectile function in diabetic mice. METHODS: Diabetes was induced by intraperitoneal injection of streptozotocin into 8-week-old C57BL/6 male mice. At 8 weeks after the induction of diabetes, the animals were distributed into 3 groups: control nondiabetic mice and diabetic mice receiving two successive intracavernous injections of phosphate buffered saline (PBS) (days −3 and 0; 20 µL) or ESC-derived exosome (days −3 and 0; 1 µg in 20 µL of PBS). Two weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested and stained with antibodies to PECAM-1, smooth muscle α-actin, NG2, and βIII tubulin. We also determined angiogenic potential of ESC-derived exosome in an ex vivo aortic ring assay and in primary cultured mouse cavernous endothelial cell (MCEC) and pericyte (MCP) mono-culture or co-culture system in vitro. RESULTS: Intracavernous injections of ESC-derived exosome significantly improved erectile function in diabetic mice, which reached up to 90% of control values. ESC-derived exosome induced significant restoration of cavernous contents of endothelial cells, smooth muscle cells, pericytes, and neuronal cells in diabetic condition. Moreover, ESC-derived exosome promoted microvascular sprouting from aortic ring and accelerated tube formation in primary cultured MCEC and MCP mono-culture or co-culture system in vitro. CONCLUSIONS: ESC-derived exosome successfully restored erectile function through enhanced cavernous angiogenesis and neural regeneration in diabetic mice. Further studies are needed to clarify mechanism by which ESC-derived exosome induces neurovascular repair.