Intravenous Infusion of Bone Marrow–Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats

Matsuda, Yuichi; Sasaki, Masanori; Kataoka‐Sasaki, Yuko; Takayanagi, Akio; Kobayashi, Ko; Oka, Shinichi; Nakazaki, Masahito; Masumori, Naoya; Kocsis, Jeffery D.

doi:10.1016/j.esxm.2017.10.005

Cited by 25 publications

(30 citation statements)

References 28 publications

(40 reference statements)

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“…Puissant and his colleagues suggested Nrf2 specificity to combine in P62 promoter of the antioxidant response element, promote the expression of P62, then combine with LC3, and activate autophagy [29]. Chunjuan Song and colleagues found that autophagy under oxidative stress was thought to be self-regulation of cells against harmful stimuli [30]. Our results suggest that probucol could increase Beclin1 and LC3-II levels and decrease the levels of P62 under oxidative stress.…”

Section: Discussionmentioning

confidence: 58%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 58%

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

et al. 2020

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“…Intravenous infusion of green fluorescent protein (GFP)-labelled allogeneic BMSCs was also effective in preventing corpora cavernosa fibrosis in a bCNI rat model 143 . Interestingly, following infusion, BMSC homing to the MPGs and injured cavernous nerves was observed.…”

Section: Effect On Fibrosis Refsmentioning

confidence: 99%

The mechanisms and potential of stem cell therapy for penile fibrosis

2018

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| Fibrosis is often caused by chronic tissue injury leading to a persisting inflammatory response with excessive accumulation of extracellular connective tissue proteins. Peyronie's disease, urethral stricture and penile (corpora cavernosa) fibrosis are localized fibrotic disorders of the penile connective tissues that can substantially impair a patient's quality of life. Research over the past few decades has revealed the ability of stem cells to secrete a wide range of paracrine factors, a characteristic that could be exploited therapeutically to prevent and treat several inflammatory and fibrotic diseases. In preclinical studies, mesenchymal stem cells (MSCs) have proven to be the most effective and readily available type of stem cells for therapeutic use. An important advantage of MSCs is their ability to circumvent the immune system and function as immunomodulatory 'drug stores' to influence multiple cell types simultaneously. Many studies using stem cells have been applied exclusively to corpora cavernosa fibrosis owing to its well-established disease models. A plethora of preclinical data suggest the benefit of stem cells for use in penile fibrosis. However, their exact mechanism of action and optimal timing and mode of administration must be determined before clinical translation.

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“…Puissant and his colleagues suggested that Nrf2 speci city to combine in P62 promoter of the antioxidant response element, promote the expression of P62, then combine with LC3 and activate autophagy [29]. Chunjuan Song and colleagues found that autophagy under oxidative stress was thought to be self-regulation of cells against harmful stimuli [30]. Our results suggest that probucol could increase Beclin1 and LC3-II levels and decrease the levels of P62 under oxidative stress.…”

Section: Discussionmentioning

confidence: 57%

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

Wang

Zhang

Ruan

et al. 2020

Preprint

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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 fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of probucol combined with MSCs. Methods: In vivo study, total forty-eight 10-week-old male Sprague-Dawley (SD) rats were used in this study. Twelve rats received intraperitoneal injection of PBS as Sham Group; the rest received intraperitoneal injection of 60mg/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), and 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 vitro experiment, H2O2 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.Results: Recovery of erectile function was observed in the P+M Group. The combination therapy decreased fibrosis and increased endothelial function compared with MSCs therapy alone. Western blotting results confirmed the increased expression of Nrf2 and HO-1 in cavernous body. H2O2 induced high oxidative stress and reduced cell viability in vitro, which was gradually reversed with increased concentration of probucol. H2O2 reduced Nrf2 expression, which was reversed by probucol's intervention. Furthermore, the expression of Bax, Caspase3 and Cleaved-Caspase3 decreased, and the expression of Bcl-2 increased in a dose-dependent manner because of probucol's intervention. In addition, Beclin1 and LC3II both increased in a dose-dependent manner. Meanwhile, the expression of P62 decreased. In study of autophagy flux, we found probucol didn’t block it. Conclusion: Probucol enhanced therapeutic efficiency of MSCs in DMED by prolonging their survival time, which mediated through improving the transplanted microenvironment of MSCs, increasing self-antioxidant ability of MSCs, strengthening protective autophagy and inhibiting apoptosis of MSCs via Nrf2 pathway.

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Intravenous Infusion of Bone Marrow–Derived Mesenchymal Stem Cells Reduces Erectile Dysfunction Following Cavernous Nerve Injury in Rats

Cited by 25 publications

References 28 publications

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

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

The mechanisms and potential of stem cell therapy for penile fibrosis

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

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