Presentation Authors: Anita Limanjaya, Mi-Hye Kwon, Kang-Moon Song, Kalyan Ghatak, Nguyen Nhat Minh, Min-Ji Choi, Jiyeon Ock, Guo Nan Yin, Ji-Kan Ryu, Jun-Kyu Suh*, Incheon, Korea, Republic of
Introduction: Recent studies have demonstrated the therapeutic potential of exosomes as bio-nanoparticles in a variety of animal models for cardiovascular diseases and neuropathies. We have found that pericytes are distributed in the erectile tissue and play important roles in regulation of penile erection, including promoting angiogenesis and neural regeneration through interacting with endothelial cells (Sci Rep 2015, Diabetes 2018). The aim of this study was to investigate effectiveness of pericyte (PC)-derived exosome in restoring erectile function in diabetic mice.
Methods: PCs were harvested from mouse corpus cavernosa and cultured. The cell suspension was sequentially extruded through ultrafine filtering and two-step OptiPrep gradient technique to acquire purified exosomes as nanovesicles. 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 PBS (days -3 and 0; 20 Î¼L or PC-derived exosome (days -3 and 0; 5 Î¼g in 20 Î¼L of PBS). Two week 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 Î±-actin, NG2, and Î²III-tubulin. We also determined angiogenic potential of PC-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 PC-derived exosome significantly improved erectile function in diabetic mice, which reached up to 91% of control values. PC-derived exosome induced significant restoration of cavernous contents of endothelial cells, smooth muscle cells, pericytes, and neuronal cells in diabetic condition. Moreover, PC-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: PC-derived exosome successfully restored erectile function through enhanced cavernous angiogenesis and neural regeneration in diabetic mice. Intracavernous delivery of exosomes derived from cavernous tissue can be a good strategy for the treatment of intractable ED in a near future.
Source of Funding: This work was supported by a National Research Foundation of Korea (NRF) grant (Jun-Kyu Suh, 2018R1A2B2002955).