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Exosomes, nanosized particles involved in many physiological and pathological processes, may become a promising tool for DMED treatment. In this study, we investigated the therapeutic effect of exosomes derived from corpus cavernosum smooth muscle cells (CCSMC\u2010EXOs) on erectile function in a rat model of diabetes and compared their effect with that of exosomes derived from mesenchymal stem cells (MSC\u2010EXOs). We incubated labelled CCSMC\u2010EXOs and MSC\u2010EXOs with CCSMCs and then observed uptake of the exosomes at different time points using laser confocal microscopy. CCSMC\u2010EXOs were more easily taken up by CCSMCs. The peak concentration and retention time of labelled CCSMC\u2010EXOs and MSC\u2010EXOs in the corpus cavernosum of DMED rats after intracavernous injection were compared by in vivo imaging techniques. Intracavernous injection of CCSMC\u2010EXOs was associated with a relatively high peak concentration and long retention time. Our data showed that CCSMC\u2010EXOs could improve erectile function in DMED rats. Meanwhile, CCSMC\u2010EXOs could exert antifibrotic effects by increasing the smooth muscle content and reducing collagen deposition. CCSMC\u2010EXOs also increased the expression of eNOS and nNOS, followed by increased levels of NO and cGMP. These findings initially identify the possible role of CCSMC\u2010EXOs in ameliorating DMED through inhibiting corporal fibrosis and modulating the NO\/cGMP signalling pathway, providing a theoretical basis for a breakthrough in the treatment of DMED.<\/jats:p>","DOI":"10.1111\/jcmm.15946","type":"journal-article","created":{"date-parts":[[2020,10,3]],"date-time":"2020-10-03T07:15:50Z","timestamp":1601709350000},"page":"13289-13302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Exosomes derived from smooth muscle cells ameliorate diabetes\u2010induced erectile dysfunction by inhibiting fibrosis and modulating the NO\/cGMP pathway"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6715-2813","authenticated-orcid":false,"given":"Jingyu","family":"Song","sequence":"first","affiliation":[{"name":"Department of Urology and Institute of Urology Tongji Hospital Tongji Medical College 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