Smooth Muscle Progenitor Cells Preserve the Erectile Function by Reducing Corporal Smooth Muscle Cell Apoptosis after Bilateral Cavernous Nerve Crush Injury in Rats.

Yi-No Wu,Chun-Hou Liao,Han-Sun Chiang,Chien-Liang Liu,Kuo-Chiang Chen

doi:10.1155/2019/8520523

Abstract

Radical prostatectomy causes erectile dysfunction (ED) and irreversible morphologic changes, including induction of endothelial and smooth muscle cell (SMC) apoptosis in the corpus cavernosum (CC). The injection of smooth muscle progenitor cells (SPCs) thickens the vascular intima and has demonstrated therapeutic benefit in cardiovascular disease animal. Herein, we investigated the effect of SPCs on the recovery of erectile function (EF) in rat models with bilateral cavernous nerve (CN) injury. Twenty-four male Sprague-Dawley rats were randomized into sham, vehicle only, or SPC treatment groups. Rats in the SPC treatment and vehicle groups were subjected to bilateral CN injury before intracavernosal injection. Intracavernosal injections of SPCs increased all EF parameters at day 28 after injury and simultaneously reduced apoptosis of the SMCs. Ultrastructural analysis revealed that SPCs maintained the integrity of the CC by preserving the structure of the adherens junctions. Tracking transplanted SPCs labeled with EdU showed that transplanted SPCs remained in the CC 28 days after treatment. Intracavernosal SPC injection restored EF after bilateral CN injury by reducing SMC apoptosis, which favored the maintenance of the structure of adherens junctions and regulated the stability of corporal vessels. These findings demonstrate the therapeutic potential of SPCs for treating ED in humans.

Highlights

Postprostatectomy erectile dysfunction (ED) complication occurring after radical prostatectomy (RP) for earlier prostate cancer is a topic of most concern
Given that smooth muscle progenitor cells (SPCs) can enhance the efficiency of proangiogenic cell-based therapy [17], the present study aimed to evaluate the therapeutic potential of SPCs injections into the corpora cavernosa of rats with bilateral cavernous nerve (CN) injury
Treatment with PDE5 inhibitors increases concentrations of cyclic guanosine monophosphate; the composition of the corporal smooth muscle cell (SMC) will limit the effects of cGMP. erefore, the main pathway of PDE5 inhibitor activity is disturbed in conditions of corporal SMC fibrosis. is may explain the low success rate of PDE5 inhibitors in treating post-RP ED

Summary

Introduction

Postprostatectomy erectile dysfunction (ED) complication occurring after radical prostatectomy (RP) for earlier prostate cancer is a topic of most concern. Nerve injury may be the main cause of erectile dysfunction after surgery [1, 2]. E PDE5 inhibitors showed benefit only in 54% of ED patients in one study [5]. Our previous study was mainly to find the advance methods to protect the cavernous nerve because a neurogenic component likely plays an important role in the pathogenesis of the ED [7,8,9]. Is suggests that the protection of the corpus SMCs from apoptosis may represent a more important treatment modality than nerve protection in future studies using the CN crush injury model [10]. Erefore, an alternative treatment is highly desirable to develop an effective, clinical feasible medication for ED patients after RP Defects in the corporal SMCs were irreversible after CN injury. is suggests that the protection of the corpus SMCs from apoptosis may represent a more important treatment modality than nerve protection in future studies using the CN crush injury model [10]. erefore, an alternative treatment is highly desirable to develop an effective, clinical feasible medication for ED patients after RP

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Discussion

Conclusion