BMSCs transplantation combined with LIPUS treatment improves erectile function through downregulation of IGFBP3 in rats with cavernosa injury.

IF 3.2 2区 医学 Q1 ANDROLOGY
Andrology Pub Date : 2024-11-21 DOI:10.1111/andr.13809
Hongen Lei, Hu Han, Jiaxing Li, Zelin Li, Renjie Li, Long Tian
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Abstract

Background: Erectile dysfunction (ED) is the most common type of sexual dysfunction, which seriously affects male reproductive health. Recently, stem cell therapy and low-intensity pulsed ultrasound (LIPUS) have been applied in the treatment of ED, but the specific mechanism is still unclear.

Objectives: The study aims to investigate the effect and underlying mechanism of further LIPUS treatment on the basis of bone marrow mesenchymal stem cells (BMSCs) transplantation in the treatment of ED rats.

Materials and methods: We established a cavernosa injury-induced ED rat model and injected BMSCs into the penile corpus cavernosum with or without LIPUS treatment every other day for three times. The survival rate of BMSCs, value of ICP/MAP, blood flow, the endothelial content, and expression of CD31 and ɑ-SMA in the rat penis were investigated. Transcriptome analyses and in vitro assays of cell proliferation, migration, and tube formation were also performed.

Results: The results showed that LIPUS treatment significantly promoted the survival rate of BMSCs in the rat penis after 1, 7, and 14 days of final treatment. The values of ICP/MAP and blood flow in rats treated with BMSCs were significantly increased compared to the control group, and the values were further enhanced in rats treated with BMSCs plus LIPUS. The endothelial content and CD31 and ɑ-SMA mRNA and protein expression in the BMSCs plus LIPUS group were remarkably higher than in other groups, indicating improved endothelial vascular function. Transcriptome analyses found that insulin-like growth factor binding protein-3 (IGFBP3) was remarkably downregulated in the BMSCs plus LIPUS group compared to the other two groups. In in vitro assays, LIPUS intervention significantly increased BMSCs proliferation and HUVECs migration, and HUVECs angiogenesis was improved after IGFBP3 siRNA transfection.

Conclusions: BMSCs transplantation combined with LIPUS treatment could improve erectile function in ED rats via downregulation of IGFBP3, which might be a proposed optimized strategy for the ED treatment.

BMSCs 移植联合 LIPUS 治疗可通过下调 IGFBP3 改善海绵体损伤大鼠的勃起功能。
背景:勃起功能障碍(ED)是最常见的性功能障碍类型,严重影响男性生殖健康。最近,干细胞疗法和低强度脉冲超声(LIPUS)被应用于治疗 ED,但其具体机制仍不清楚:本研究旨在探讨在骨髓间充质干细胞(BMSCs)移植的基础上进一步采用 LIPUS 治疗 ED 大鼠的效果及其内在机制:建立阴茎海绵体损伤诱导的ED大鼠模型,将骨髓间充质干细胞(BMSCs)注射到阴茎海绵体内,每隔一天注射一次或不注射LIPUS,共注射三次。研究了大鼠阴茎中 BMSCs 的存活率、ICP/MAP 值、血流量、内皮含量以及 CD31 和 ɑ-SMA 的表达。此外,还进行了转录组分析以及细胞增殖、迁移和管形成的体外试验:结果:结果表明,LIPUS 处理大鼠阴茎 1、7 和 14 天后,能显著提高 BMSCs 的存活率。与对照组相比,用 BMSCs 处理的大鼠的 ICP/MAP 值和血流量均明显增加,而用 BMSCs 加 LIPUS 处理的大鼠的 ICP/MAP 值和血流量则进一步增加。BMSCs 加 LIPUS 组的内皮含量、CD31 和 ɑ-SMA mRNA 和蛋白表达量明显高于其他组,表明内皮血管功能得到改善。转录组分析发现,与其他两组相比,BMSCs 加 LIPUS 组的胰岛素样生长因子结合蛋白-3(IGFBP3)明显下调。在体外实验中,LIPUS的干预明显增加了BMSCs的增殖和HUVECs的迁移,IGFBP3 siRNA转染后,HUVECs的血管生成得到改善:结论:BMSCs移植联合LIPUS治疗可通过下调IGFBP3改善ED大鼠的勃起功能,可能是治疗ED的一种优化策略。
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来源期刊
Andrology
Andrology ANDROLOGY-
CiteScore
9.10
自引率
6.70%
发文量
200
期刊介绍: Andrology is the study of the male reproductive system and other male gender related health issues. Andrology deals with basic and clinical aspects of the male reproductive system (gonads, endocrine and accessory organs) in all species, including the diagnosis and treatment of medical problems associated with sexual development, infertility, sexual dysfunction, sex hormone action and other urological problems. In medicine, Andrology as a specialty is a recent development, as it had previously been considered a subspecialty of urology or endocrinology
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