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AB184. Effects of target gene expression on ex vivo differentiated mesenchymal stromal cells transfected by lent viral vector with PDE5 of short hairpin RNA

机译:AB184。靶基因表达对短发夹RNA PDE5慢病毒载体转染离体分化的间充质基质细胞的影响

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摘要

IntroductionIt has been shown that the major causes of erectile dysfunction (ED) associated with aging were via a diffuse and progressive corporal fibrosis to cavernous smooth muscle cells (CSMCs) in the penis. Previous studies have demonstrated that bone marrow-mesenchymal stromal cells (BM-MSCs) could possess the ability for self-renewal, multiline age differentiation and in vivo functional regeneration of damaged tissues. It was suggested that they be induced to differentiate into smooth muscle-like cells in vitro and have a potential source for stem-cell-based gene therapy of ED. Specific phosphodiesterases (PDE5) has been proved to play an important role in regulating penile erection to return to flaccidity by hydrolysis of cyclic guanosine monophosphate (cGMP) as a specific hydratase. Therefore, inhibiting specifically the catalytic activity of the target gene PDE5 has been indicated to promote the accumulation of cGMP and enhance erection. In recent years, the introduction of short hairpin RNA (shRNA) has proved to be a powerful tool for suppressing strongly gene specific expression through a process known as RNA interference. This study was to describe that stem cell-based replacement therapy with rat BM-MSCs by transfected the lentiviral vector carrying silencing target gene PDE5 of short hairpin RNA (PDE5-shRNA) could aid in the regeneration of penile smooth musculature and might help to benefit recovery of erectile function.
机译:引言研究表明,与衰老相关的勃起功能障碍(ED)的主要原因是通过阴茎中的海绵体平滑肌细胞(CSMC)扩散和进行性体纤维化。先前的研究表明,骨髓间质基质细胞(BM-MSC)可能具有自我更新,多系年龄分化和受损组织的体内功能再生的能力。提示它们在体外被诱导分化为平滑肌样细胞,并为基于干细胞的ED基因治疗提供了潜在来源。特定的磷酸二酯酶(PDE5)已被证明在通过调节环状鸟苷单磷酸(cGMP)作为特定的水合酶而调节阴茎勃起并恢复松弛状态中起重要作用。因此,已经表明特异性抑制靶基因PDE5的催化活性可促进cGMP的积累并增强勃起。近年来,短发夹RNA(shRNA)的引入已被证明是通过称为RNA干扰的过程抑制强烈的基因特异性表达的强大工具。这项研究的目的是通过转染携带短发夹RNA沉默靶基因PDE5的慢病毒载体(PDE5-shRNA)的大鼠BM-MSC进行的干细胞替代疗法可以帮助阴茎平滑肌组织再生恢复勃起功能。

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