Exosomes derived from smooth muscle cells ameliorate diabetes‐induced erectile dysfunction by inhibiting fibrosis and modulating the NO/cGMP pathway

Abstract

Erectile dysfunction (ED) is a major health issue among men with diabetes, and ED induced by diabetes mellitus (DMED) is particularly difficult to treat. Therefore, novel therapeutic approaches for the treatment of DMED are urgently needed. 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‐EXOs) on erectile function in a rat model of diabetes and compared their effect with that of exosomes derived from mesenchymal stem cells (MSC‐EXOs). We incubated labelled CCSMC‐EXOs and MSC‐EXOs with CCSMCs and then observed uptake of the exosomes at different time points using laser confocal microscopy. CCSMC‐EXOs were more easily taken up by CCSMCs. The peak concentration and retention time of labelled CCSMC‐EXOs and MSC‐EXOs in the corpus cavernosum of DMED rats after intracavernous injection were compared by in vivo imaging techniques. Intracavernous injection of CCSMC‐EXOs was associated with a relatively high peak concentration and long retention time. Our data showed that CCSMC‐EXOs could improve erectile function in DMED rats. Meanwhile, CCSMC‐EXOs could exert antifibrotic effects by increasing the smooth muscle content and reducing collagen deposition. CCSMC‐EXOs 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‐EXOs 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.

Stem cell therapy and diabetic erectile dysfunction: A critical review

“…However, the number of cells injected among these studies ranged from 2 × 10 6 to 5 × 10 5 cells per animal[ 46 , 47 ]. Moreover, in addition to stem cell therapy, several studies added growth factors, hormones and drugs, including insulin[ 48 ], magnetic iron oxide nanoparticles[ 49 ], microtissue[ 50 ], inducible NOS[ 47 ], myocardin[ 51 ], icariin[ 52 ], corin[ 53 ], exosomes from corpus cavernosum smooth muscle cells[ 54 ], fibroblast growth factor 2 (FGF2)[ 55 ], stromal cell-derived cell factor-1 (SDF-1)[ 56 ], VEGF[ 57 ] and hepatocyte growth factor[ 45 ].…”

Plasma‑derived exosomal pyruvate kinase isoenzyme type M2 accelerates the proliferation and motility of oesophageal squamous cell carcinoma cells

“…Other studies ( 29 , 30 ) and our previous study ( 31 – 33 ) have shown that the expression of PKM2 in tumour tissues and cells was higher than that in normal-adjacent tissues and oesophageal epithelial cells, and that upregulation of the PKM2 isoform was associated with the increased Warburg effect of tumour cells ( 34 , 35 ). Moreover, exosomes express blastocyte-derived surface markers ( 36 ). Cancer cells, which secrete more exosomes than normal tissue cells ( 37 ), secrete elevated levels of PKM2.…”

Exosomes Derived by SIRT1-Overexpressing Bone Marrow Mesenchymal Stem Cells Improve Pubococcygeus Muscle Injury in Rats

“…It has been shown that Exos exert positive effects in proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (24). Exos derived from BMSCs prompt activation of microvascular endothelial cells in cerebral ischemia/reperfusion injury and attenuated diabetes-induced erectile dysfunction (25,26). Therefore, we hypothesized that Exos might also have an effect on SUI.…”