Apoptosis and Effects of Intracavernous Bone Marrow Cell Injection in a Rat Model of Postprostatectomy Erectile Dysfunction

Fall, Papa Ahmed; Izikki, Mohamed; Tu, Ly; Swieb, Salem; Giuliano, François; Bernabé, Jacques; Souktani, Rachid; Abbou, Claude C.; Adnot, Serge; Eddahibi, Saadia; Yiou, R.

doi:10.1016/j.eururo.2008.09.059

Cited by 79 publications

(67 citation statements)

References 29 publications

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“…These results mean that it is impossible to restore SMC spontaneously after CN injury and that a normal apoptotic index does not result in the normal contents of SMC. In this study, similar to the results from previous studies, 8,9,19 western blot analysis showed a transient decrease in expression of penile phospho-Akt and phospho-eNOS at 1 week after CN resection or crush injury. On the other hand, our results showed that MYPT1 phosphorylation, a surrogate for ROCK activity, progressively increased over the course of time after bilateral CN resection or crush injury, possibly contributing to persistent impairment of erectile function throughout the experimental period.…”

Section: Discussionsupporting

confidence: 80%

“…8 Bilateral CN ablation was followed by transient drops in eNOS and neuronal nitric oxide synthase (nNOS), contrasting with prolonged impairment of erectile function. 9 Recently, it has been suggested that decreased erectile function after a CN crush injury is accompanied by the up-regulation of the RhoA/Rho-kinase (ROCK) pathway in the rat penis. 10,11 However, there has been a scarcity of integrated, long-term (＞4 week) studies on structural and functional alterations in the penis according to the period following CN injury.…”

Section: Introductionmentioning

confidence: 99%

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Is It Possible to Recover Erectile Function Spontaneously after Cavernous Nerve Injury? Time-Dependent Structural and Functional Changes in Corpus Cavernosum Following Cavernous Nerve Injury in Rats

et al. 2012

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= Abstract =Purpose: There has been a scarcity of integrated, long-term (＞4 week) studies on structural and functional alterations in the penis according to the period following cavernous nerve (CN) injury. The aim of this study was to investigate time-dependent structural and functional changes in the corpus cavernosum following CN injury in a rat model. Materials and Methods:Ninety male Sprague-Dawley rats (10 weeks old) were divided into 4 groups: normal control (C), sham (S), bilateral CN resection (R), and bilateral CN crush injury (I) groups. At 1, 4, and 12 weeks after the procedure, erectile function was assessed by electrostimulation. The terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay was performed for detection of apoptosis. Masson's trichrome staining and immunohistochemistry were performed for detection of alpha smooth muscle actin (α-SMA). Western blot analysis was then performed. Results:The R and I groups showed persistent impairment of erectile function at all three points in time. Apoptosis peaked at 1 week after resection or crush injury and then gradually subsided. The smooth muscle cell/collagen ratio and expression of α-SMA gradually decreased over time after CN resection or crush injury. Myosin phosphatase target subunit 1 phosphorylation progressively increased over time after CN resection or crush injury. On the other hand, expression of phospho-protein kinase B, phospho-endothelial nitric oxide synthase, and neuronal nitric oxide synthase transiently decreased at 1 week after resection or crush injury and then recovered to the control values. Conclusions:Our results suggest that persistent up-regulation of the RhoA/Rho-kinase pathway and structural change such as decreased smooth muscle cell and increased cavernosal fibrosis might play an important role in persistent erectile dysfunction following CN injury.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Is It Possible to Recover Erectile Function Spontaneously after Cavernous Nerve Injury? Time-Dependent Structural and Functional Changes in Corpus Cavernosum Following Cavernous Nerve Injury in Rats

et al. 2012

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“…In 2008, Nolazco et al [80] indicated that intracavernous injection of SkMSC could restore cavernous SMC and erectile function in aged rats. In 2009, Fall et al [28] reported that intracavernous injection of BMSC improved erectile function in a rat model of postprostatectomy ED.…”

Section: Penismentioning

confidence: 98%

Adipose-Derived Stem Cells: Characterization and Application in Urology

Lin

Lue

2011

Adipose Stem Cells and Regenerative Medicine

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“…More importantly, allogeneic MSCs can also achieve successful transplantation [12] as the result of a low immunogenicity of the cells [13], which largely extends the usage of MSCs. As for ED therapy, MSCs implantation has been proved to significantly improve the recovery of erectile function in animal studies [14] by inhibiting apoptosis [15]. Focusing on the diabetic ED, MSCs based treatment also received encouraging therapeutic effects [16].…”

Section: Introductionmentioning

confidence: 99%

Combination of mesenchymal stem cell injection with icariin for the treatment of diabetes-associated erectile dysfunction

Wang

Liu

et al. 2017

PLoS ONE

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The present study was aimed to examine whether icariin, a traditional Chinese medicine, could improve therapeutic effects of adipose derived mesenchymal stem cells (ADSCs) for diabetes-associated erectile dysfunction (DMED). DMED were induced in rats by intraperitoneal injection of streptozotocin and confirmed by erectile function measurement. Then, rats of diabetic ED were randomly divided to receive the treatment of saline, ADSCs, icariin or ADSCs combined with icariin respectively. Compared with the treatment by ADSCs or icariin alone, intracavernosum injection of ADSCs combined with the following daily gastric gavage of icariin significantly augmented the value of ICP and ICP/MAP (p<0.01). Meanwhile, the survival of transplanted ADSCs was much improved due to the application of icariin. Similarly, immunofluorescent staining analysis demonstrated that the improved erectile tissue structure by combination of ADSCs and icariin was significantly associated with the increased expression of endothelial markers (vWF) (p<0.01) and smooth muscle markers (α-SMA) (p<0.01). Furthermore, the structure changes in corpus cavernosum were further confirmed by the Masson’s trichrome staining. To explore the possible mechanism underlying icariin-enhanced therapeutic efficacy of MSCs, we employed an in vitro testing system by introducing H2O2 to imitate oxidative stress condition considering the oxidative environment faced by engrafted ADSCs and anti-oxidative capacity of icariin. In vitro, we found that the addition of icariin considerably reduced the apoptosis of ADSCs, and attenuated the intracellular reactive oxygen species (ROS), the superoxidase dismutase (SOD) activity and the lactate dehydrogenase (LDH). Subsequently, we examined the expression of apoptosis-related proteins and explored the potential signaling pathway through which icariin promoted the survival of ADSCs against oxidative stress. It was demonstrated that icariin significantly inhibited the upregulation of apoptosis-related proteins under oxidative condition, including Bax and cleaved caspase-3, while promoted the expression of anti-apoptotic factor BCL2. These effects were accompanied with the activation of signal molecules, PI3K/Akt and STAT3. The further signal protein inhibition assays exhibited that the suppression of STAT3 abrogated the icariin-mediated anti-apoptotic effects observed above, while did not influence the expression of PI3K/Akt. However, PI3K inhibition could abrogate icariin–mediated STAT3 activation and achieved a similar effect as STAT3 inhibition. Our results suggested that icariin was an effective adjuvant for enhancing ADSC-based therapy of DMEM, which may be ascribed to their protection of ADSCs against oxidative stress via the regulation of PI3K/Akt-STAT3 signal pathway.

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Apoptosis and Effects of Intracavernous Bone Marrow Cell Injection in a Rat Model of Postprostatectomy Erectile Dysfunction

Cited by 79 publications

References 29 publications

Is It Possible to Recover Erectile Function Spontaneously after Cavernous Nerve Injury? Time-Dependent Structural and Functional Changes in Corpus Cavernosum Following Cavernous Nerve Injury in Rats

Is It Possible to Recover Erectile Function Spontaneously after Cavernous Nerve Injury? Time-Dependent Structural and Functional Changes in Corpus Cavernosum Following Cavernous Nerve Injury in Rats

Adipose-Derived Stem Cells: Characterization and Application in Urology

Combination of mesenchymal stem cell injection with icariin for the treatment of diabetes-associated erectile dysfunction

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