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.

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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