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Published on: January 12, 2024
Adipose Mesenchymal Stromal Cell-Derived Exosomes Prevent Testicular Torsion Injury via Activating PI3K/AKT and
Hengchen Liu1, Manyu Shi1, Xiangqi Li1
1Department of Pediatric Surgery, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin 150001, China.
Abstract:
Adipose mesenchymal stromal cell-derived exosomes (ADSC-Exos) have shown great potential in the treatment of oxidative stress induced by ischemia-reperfusion injury. However, alleviation of testicular torsion injury by ADSC-Exos has not been reported. Therefore, we investigated the protective effect of ADSC-Exos against testicular torsion-detorsion injury. ADSC-Exos were isolated by ultracentrifugation and injected into torsion-detorsion-affected testes of rats. H&E staining and sperm quality were used to evaluate the therapeutic effects of ADSC-Exos, and tissue oxidative stress was measured by determining MDA and SOD levels. In addition, TUNEL staining and immunohistological analysis (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 predicted signaling pathways were validated in vitro by assessing the proliferation (EdU assay), migration (transwell assay and scratch test), and apoptosis (flow cytometry, TUNEL staining, and western blotting) of spermatogenic cells. The results showed that ADSC-Exos alleviated testicular torsion-detorsion injury by attenuating oxidative stress and the inflammatory response. 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.
Insights
Adipose mesenchymal stromal cell-derived exosomes (ADSC-Exos) protect against testicular torsion injury by reducing oxidative stress and inflammation. These exosomes promote spermatogenic cell survival and function via PI3K/AKT and MAPK/ERK signaling.
Area of Science:
- Regenerative Medicine
- Male Reproductive Health
- Cell Biology
Background:
- Ischemia-reperfusion injury in testes causes significant damage.
- Adipose mesenchymal stromal cell-derived exosomes (ADSC-Exos) show promise in treating oxidative stress.
- The therapeutic potential of ADSC-Exos for testicular torsion injury remains unexplored.
Purpose of the Study:
- To investigate the protective effects of ADSC-Exos against testicular torsion-detorsion injury in a rat model.
- To elucidate the mechanisms underlying ADSC-Exos' therapeutic actions on testicular tissue and spermatogenic cells.
Main Methods:
- ADSC-Exos were isolated and administered to rats with torsion-detorsion injury.
- Histopathological (H&E), sperm quality, oxidative stress (MDA, SOD), apoptosis (TUNEL), and inflammatory markers (IL-6, IL-10) were assessed.
- Immunohistochemistry (Ki67, Cleaved Caspase-3, CCR7, CD163) and bioinformatics analysis were performed.
- In vitro studies validated signaling pathways (PI3K/AKT, MAPK/ERK1/2) using EdU, transwell, scratch, flow cytometry, and western blotting.
Main Results:
- ADSC-Exos treatment significantly alleviated testicular torsion-detorsion injury.
- Exosomes attenuated oxidative stress and inflammatory responses within testicular tissue.
- ADSC-Exos promoted spermatogenic cell proliferation and migration while inhibiting apoptosis.
- Activation of PI3K/AKT and MAPK/ERK1/2 signaling pathways was confirmed as the underlying mechanism.
Conclusions:
- ADSC-Exos demonstrate significant therapeutic potential for testicular torsion-detorsion injury.
- The protective effects are mediated by reducing oxidative stress, inflammation, and apoptosis, alongside promoting cell proliferation and migration.
- Targeting PI3K/AKT and MAPK/ERK1/2 pathways offers a novel therapeutic strategy for testicular protection.
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