BACKGROUND Aging is one of the dominant factors contributing to erectile dysfunction (ED), and effective treatments for age-associated ED are urgently demanded. In this study, the therapeutic efficiency of bone marrow-derived mesenchymal stem cells (BMSCs) overexpressing microRNA-145 (miR-145) was evaluated in ED. METHODS Sixty male Sprague-Dawley rats (24 months old) were randomly divided into 4 treatment groups (n = 15/group): PBS (control), BMSCs, BMSCs transfected with a blank vector (vector-BMSCs), and BMSCs transfected with a lentivirus overexpressing miR-145 (OE-miR-145-BMSCs). Fourteen days after transplantation of BMSCs, erectile function was evaluated by measuring intra-cavernous pressure (ICP) and mean arterial pressure (MAP). Subsequently, penile erectile tissues were harvested and subjected to Masson staining, qRT-PCR, immunofluorescence staining, dual luciferase assay, and Western blot analysis. RESULTS Fourteen days after transplantation, the ICP/MAP was 0.79 ± 0.05 in the OE-miR-145-BMSC group, 0.61 ± 0.06 in the BMSC group, 0.57 ± 0.06 in the vector-BMSC group, and 0.3 ± 0.01 in the PBS group. Treatment with OE-miR-145-BMSCs significantly improved ED (P < 0.05), and the treatment increased the smooth muscle content in the penis tissues of ED rats (P < 0.05). In the OE-miR-145-BMSC group, the expression levels of α-SMA, desmin, and SM-MHC were higher than they were in the other ED groups (P < 0.05). In addition, the levels of collagen 1, MMP2, and p-Smad2 in the BMSC-treated group, especially in the OE-miR-145-BMSC group, were lower than those in the control group (P < 0.05). CONCLUSIONS MicroRNA-145 engineered BMSCs effectively attenuate age-related ED. Transplantation of miR-145-overexpressing BMSCs may provide a promising novel avenue for age-associated ED therapy.

中文翻译：

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MicroRNA-145工程改造的骨髓间充质干细胞减轻了老年大鼠的勃起功能障碍。

背景技术衰老是导致勃起功能障碍（ED）的主要因素之一，因此迫切需要有效的治疗与年龄相关的ED的方法。在这项研究中，在ED中评估了过表达microRNA-145（miR-145）的骨髓间充质干细胞（BMSC）的治疗效率。方法将60只雄性Sprague-Dawley大鼠（24个月大）随机分为4个治疗组（n = 15 /组）：PBS（对照组），BMSCs，用空白载体转染的BMSCs（vector-BMSCs）和转染BMSCs的BMSCs。一种过表达miR-145的慢病毒（OE-miR-145-BMSC）。BMSCs移植后第14天，通过测量海绵体内压力（ICP）和平均动脉压（MAP）评估勃起功能。随后，收获阴茎勃起组织并进行Masson染色，qRT-PCR，免疫荧光染色，双重荧光素酶测定和蛋白质印迹分析。结果移植后14天，OE-miR-145-BMSC组的ICP / MAP为0.79±0.05，BMSC组的为ICP / MAP为0.61±0.06，载体BMSC组的为ICP / MAP为0.57±0.06，PBS为0.3±0.01团体。OE-miR-145-BMSCs治疗可显着改善ED（P <0.05），并且治疗可增加ED大鼠阴茎组织中的平滑肌含量（P <0.05）。在OE-miR-145-BMSC组中，α-SMA，结蛋白和SM-MHC的表达水平高于其他ED组（P <0.05）。另外，BMSC治疗组，尤其是OE-miR-145-BMSC组的胶原1，MMP2和p-Smad2水平低于对照组（P <0.05）。结论MicroRNA-145工程化的骨髓间充质干细胞可有效减弱与年龄有关的ED。过度表达miR-145的BMSC的移植可能为年龄相关性ED治疗提供有希望的新途径。