Treatment of diabetes mellitus-induced erectile dysfunction using endothelial progenitor cells genetically modified with human telomerase reverse transcriptase.

Treatment of diabetes mellitus-induced erectile dysfunction using endothelial progenitor cells genetically modified with human telomerase reverse transcriptase.
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使用经人端粒酶逆转录酶基因修饰的内皮祖细胞治疗糖尿病引起的勃起功能障碍。

DOI:
10.18632/oncotarget.9909
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发表时间:
2016-06-28
期刊:
影响因子:
--
通讯作者:
Ye Z
Ye Z
中科院分区:
其他
文献类型:
--
作者:
Zhang Y;Chen Z;Wang T;Yang J;Li R;Wang S;Liu J;Ye Z

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糖尿病性勃起功能障碍(DMED)的治疗效果很差,干细胞治疗正在成为一种有用的方法。在这项研究中,我们使用过表达人端粒酶逆转录酶(hTERT)的内皮祖细胞(EPCs)治疗DMED。用hTERT转染大鼠EPCs (EPCs-hTERT)。EPCs-hTERT分泌更多的生长因子,并表现出增强的增殖和抗氧化应激能力。24只雄性DMED大鼠分别给予DMED (DMED组)、EPCs (EPCs组)、EPCs- control慢病毒转导的EPCs (EPCs- control组)和EPCs- htert (EPCs- htert组)4种处理。以健康大鼠为正常对照组。与EPCs和EPCs-对照组相比,EPCs- htert组勃起功能明显增强。EPCs-hTERT组在阴茎组织中表现出更多的生长因子、平滑肌含量和保留的干细胞。EPCs-hTERT组阴茎组织细胞凋亡程度和胶原/平滑肌比值明显降低。内皮型一氧化氮合酶(eNOS)表达在EPCs-hTERT组显著升高。综上所述,这些数据表明,增强的旁分泌作用、抗氧化应激能力和EPCs-hTERT的增殖可能有助于改善DMED大鼠的勃起功能。
The efficacy of treatments for diabetes mellitus-induced erectile dysfunction (DMED) is quite poor, and stem cell therapy is emerging as a useful method. In this study, we used endothelial progenitor cells (EPCs) overexpressing human telomerase reverse transcriptase (hTERT) for the treatment of DMED. Rat EPCs were transfected with hTERT (EPCs-hTERT). EPCs-hTERT secreted more growth factors and demonstrated enhanced proliferation and resistance to oxidative stress. Twenty-four male DMED rats were subjected to four treatments: DMED (DMED group), EPCs (EPCs group), EPCs transduced with control lentivirus (EPC-control group) and EPCs-hTERT (EPCs-hTERT group). A group of healthy rats were used as the normal control group. The erectile function in the EPCs-hTERT group was markedly increased compared with the EPCs and EPCs-control groups. The EPCs-hTERT group exhibited more growth factors, smooth muscle content and retained stem cells in penile tissues. The degree of apoptosis and collagen/smooth muscle ratio in penile tissues of the EPCs-hTERT group was considerably reduced. Endothelial nitric oxide synthase (eNOS) expression increased significantly in the EPCs-hTERT group. Taken together, these data showed that the enhanced paracrine effect, resistance to oxidative stress and proliferation of EPCs-hTERT may contribute to the improvements of erectile function in DMED rats.
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