Adipose-derived mesenchymal stromal cell-derived exosomes alleviate testicular torsion injury via activation of PI3K/AKT and MAPK/ERK1/2 pathways

Abstract

Background Exosomes have became a new nano-scale therapeutic method in recent years. Adipose-derived mesenchymal stromal cell-derived exosomes (ADSC-Exos) have shown great potential in the treatment of ischemia-reperfusion injury. However, there is no research on whether ADSC-Exos can alleviate testicular torsion injury. Therefore, we investigated the protective effect of ADSC-Exos in alleviating testicular torsion-detorsion injury. Methods ADSC-Exos were isolated by ultracentrifugation and injected into the torsion-detorsion-affected testes of rats. H&E staining and sperm quality were used to evaluate the therapeutic effects of ADSC-Exos, and the level of tissue oxidative stress was determined using malondialdehyde (MDA) and superoxide dismutase (SOD). In addition, TUNEL staining and immunohistological analyses (Ki67, cleaved Caspase-3, IL-6, IL-10, CCR7, and CD163) were used to clarify the effects of ADSC-Exos on spermatogenic cell proliferation, apoptosis, and the inflammatory microenvironment in vivo . Possible signaling pathways were predicted using sequencing technology and bioinformatics analysis. The signaling pathways were validated by proliferation (EdU), migration (transwell and scratch test), and apoptosis (flow cytometry, TUNEL, and western blot) in vitro . Results ADSC-Exos alleviated testicular torsion-detorsion injury by attenuating oxidative stress and inflammatory responses. In addition, ADSC-Exos promoted the proliferation and migration of spermatogenic cells and inhibited their apoptosis by activating the PI3K/AKT and MAPK/ERK1/2 signaling pathways. Conclusions Overall, we demonstrated that ADSC-Exos can alleviate testicular torsion injury and provided a new approach for treating testicular torsion injury.