Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway

Abstract

Background: Intracavernous injection of mesenchymal stem cells (MSCs) is a promising method for diabetic mellitus-induced erectile dysfunction (DMED), but short survival time of MSCs in cavernous is a fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of probucol combined with MSCs. Methods: In vivo study, a total of forty-eight 10-week-old male Sprague-Dawley (SD) rats were used. Twelve rats received intraperitoneal injection of PBS as the sham group; the rest received intraperitoneal injection of 60 mg/kg streptozotocin to establish DM models. DM rats were randomly divided into three groups: received intracavernosal (IC) injection of either PBS (DM group), MSCs (M group), or administrated probucol after intracavernosal injection of MSCs (P + M group). Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated for histologic examination and Western blotting. In in vitro experiment, H 2 O 2 was used to create oxidative stress environment to detect changes in cell viability. CCK8 was used to measure cell viability of MSCs treated with or without probucol. Intracellular ROS changes were detected by flow cytometry. Autophagy and apoptosis were detected by Western blotting and confocal microscopy.

Umbilical Cord-Derived Mesenchymal Stem Cells Improve TGF-"&#".ord($0).";""&#".ord($0).";", "&#".ord($0).";""&#".ord($0).";"-SMA and Collagen on Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats

“…Therefore, it is necessary to conduct research and development of new therapy for DMED. Recently, stem cell therapy has been added to the treatment options for ED ( 5 , 30 , 31 ). MSCs are now considered an alternative approach to DMED with preliminary studies demonstrating their ability to stimulate smooth muscle cells and regenerate cavernous nerves ( 5 , 28 , 32 ).…”

“…ED is a more prevalent complication of diabetes mellitus (DM) in men, affecting up to 85% of DM patients ( 4 ). Diabetes mellitus-induced erectile dysfunction (DMED), more refractory than ED in nondiabetic patients, is believed to be mainly due to endothelial injury, decreased smooth muscle content, neuropathy, and fibrosis ( 5 , 6 ). Currently, the use of selective phosphodiesterase type-5 inhibitors (PDE5i) is considered to be the first-line agent for ED, however, it has much lower efficacy to treat patients with DMED ( 3 , 4 , 7 ).…”

“…A recent study revealed that transplantation of the MSCs into penile tissues of DMED rats can improve the impaired arterial flow and structural changes in erectile function ( 5 ). Another previous study also showed that intra-cavernous transplantation of VEGF gene-modified bone marrow-derived MSCs resulted in improved erectile function in diabetic rats ( 20 ).…”

Correction to: Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway

“…Following the publication of this article [ 1 ], the authors notice the immunohistochemical staining of α-SMA in Fig. 2 contains incorrect images.…”

Mesenchymal Stem Cells Enhance Vascular Endothelial Growth Factor-A, Endothelial Nitric Oxide Synthetase, and HSP70 Expression in Improving Erectile Dysfunction in Streptozotocin-induced Diabetic Rats

“…The endothelial injury, decrease of smooth muscle content, neuropathy, and fibrosis are responsible for DMED [6]. Selective phosphodiesterase type-5 inhibitors (PDE5i) constitute the first-line agent for ED; however, it has much lower efficacy in treating patients with DMED [6], [7]. In this condition, revealing the novel alternative approach is a major needed to ameliorate DMED development.…”