Research Paper|Volume 13, Issue 10|pp 14399—14415

MicroRNA-126 engineered muscle-derived stem cells attenuates cavernosa injury-induced erectile dysfunction in rats

Zihao Zou¹, Muyuan Chai², Feixiang Guo¹, Xin Fu¹, Yu Lan¹, Shuqi Cao¹, Jianan Liu¹, Long Tian³, Geng An¹

¹Center for Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China
²National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong, PR China
³Beijing Chao-Yang Hospital, Capital Medical University, Beijing, PR China

* Equal contribution

Received: July 22, 2020Accepted: November 25, 2020Published: May 23, 2021

https://doi.org/10.18632/aging.203057

Copyright: © 2021 Zou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Cavernosa injury is a common cause of organic erectile dysfunction (ED), which requires safe and effective treatments. In the present study, the therapeutic efficiency of muscle-derived stem cells (MDSCs) modified with microRNA-126 (miR-126) was determined in rats with cavernosa injury.

Methods: MDSCs were transfected with miR-126 and then were transplanted into rats with cavernosa injury. Erectile function, vascular function (western blot and immunofluorescence), extraction, and detection of exosomes were then undertaken.

Results: On the 28th day after transplantation, the highest value of intra-cavernous pressure (ICP)/mean arterial pressure (MAP) in rats of miRNA-126 group (0.84 ± 0.14) was observed (Control: 0.38 ± 0.07; MDSC: 0.54 ± 0.11, Vector: 0.60 ± 0.02; respectively). Treatment of miRNA-126-modified-MDSCs remarkably strengthened vascular structure, supported by hematoxylin-eosin staining. The expression of CD31, von Willebrand Factor and vascular endothelial factors were higher than those in other groups, indicating improved vascular function. In vitro mechanism studies showed that exosomes containing miR-126 isolated from MDSCs promoted angiogenesis and attenuated apoptosis of human umbilical venous endothelial cells. Finally, insulin receptor substrate 1 and Krüppel-like factor 10 were determined as the direct target genes of miR-126.

Conclusions: MiR-126 engineered MDSCs notably repaired cavernosa injury in rats via vascular reconstruction by directly targeting IRS1 and KLF10, in which the exosomes secreted by MDSCs played a critical role.