Abstract
Background Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED). However, the interactions and effects of action between MSCT and ESWT remain poorly understood. In this study, we investigated the mechanisms of combination therapy with MSCT and ESWT in a rat model of diabetic ED. Materials and Methods Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts. Diabetic rats induced by streptozotocin (65 mg/kg) were randomly divided into 4 groups: (1) DM control group, (2) DM + ESWT group, (3) DM + MSCT group, and (4) DM + ESWT + MSCT group. The sham group was a normal control group (without streptozotocin). MSCT and (or) ESWT were, respectively, administered to each group according to the proposal for 8 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA, and Western blotting. Results The ratio of ICP/MAP was significantly higher in the DM + ESWT + MSCT group than in ESWT or MSCT treated group (P < 0.05). Also, the treatment stimulated angiogenesis and vasodilatation in the corpus cavernosum (P < 0.05). ESWT increased the quantity of MSCs in the corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (P < 0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the corpus cavernosum. The combination approach stimulated autophagy and decreased apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the DM + ESWT + MSCT group than in the DM control group (P < 0.01). Furthermore, the treatment promoted the MSC recruitment by inducing penile tissues to express more PECAM and SDF-1. Conclusions Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future.
Highlights
Diabetic patients suffer from a higher incidence of erectile dysfunction (ED), which is less responsive to drugs than nondiabetic individuals, and this diabetes mellitus (DM) erectile dysfunction (DMED) seriously influences the quality of life of diabetic patients [1,2,3]
The ratio of intracavernous pressure (ICP)/mean arterial blood pressure (MAP) was significantly higher in the DM + energy shock wave therapy (ESWT) + Mesenchymal stem cell therapy (MSCT) group than in the DM + ESWT and DM + MSCT groups (P < 0 05)
We found that NGF (Figures 3(a) and 3(A)) and BDNF (Figures 3(c) and 3(C)) expression was higher in the DM + ESWT + MSCT group than in the DM group (P < 0 01), which has been considered to defend apoptosis [43, 44]
Summary
Diabetic patients suffer from a higher incidence of erectile dysfunction (ED), which is less responsive to drugs than nondiabetic individuals, and this diabetes mellitus (DM) erectile dysfunction (DMED) seriously influences the quality of life of diabetic patients [1,2,3]. Hayashi et al [7] reported that the expressions of various proangiogenic factors, such as vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), could be upregulated by DL-ESWT in diabetic mice Another reason for ED therapy using DL-ESWT is that it can enhance the recruitment of endothelial progenitor cells by upregulating stromal cell-derived factor-1 (SDF-1) in wound tissues [16]. Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future
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