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  3. Exosomes derived from ADSC suppress endothelial cells ferroptosis and alleviate sepsis acute liver injury via regulation of Keap1/Nrf2/GPX4 axis: an experimental study

Exosomes derived from ADSC suppress endothelial cells ferroptosis and alleviate sepsis acute liver injury via regulation of Keap1/Nrf2/GPX4 axis: an experimental study

  • Stem Cells. 2025 Sep 27:sxaf063. doi: 10.1093/stmcls/sxaf063.
Xianqi Wang 1,  Dan Wu 1,  Xiaoyang Liu 2,  Yanan Xu 1,  Peiwen Wang 1,  Heliang Fu 1,  Yuexiang Ma 1,  Shanshou Liu 1,  Qianmei Wang 1,  Xian-Jie Xu 1 3,  Zheng Dai 1,  Qi Zhang 1,  Wen Yin 1,  Kuo Shen 1 4,  Junjie Li 1
Affiliations

Affiliations

  • 1 Emergency Department, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shanxi, China.
  • 2 Department of Hepatobiliary Surgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji'nan, Shandong, China.
  • 3 Emergency Department, Air Force Medical Center, The Fourth Military Medical University, PLA, No.30 Fucheng Road, Haidian District, Beijing, 100142, China.
  • 4 Air Force Hospital of Western Theater Command, Chengdu, Sichuan, 610065, P.R. China.
PMID: 41014491 DOI: 10.1093/stmcls/sxaf063
Abstract

Background: Adipose-derived stem cells exosome (ADSC-exo) has been reported to be effective in alleviating organ dysfunction in sepsis, including acute liver injury (ALI). Whether ADSC-exo protects the liver via suppression of vascular endothelial cell (VEC) Ferroptosis is unclear.

Methods: We evaluated the viability and migration of VECs and their ferroptosis-related indices. To further elucidate this mechanism, we examined the Nrf2/GPX4 pathway. Cecal ligation and puncture (CLP) was performed to establish a sepsis model to observe the protective effect of ADSC-exo. The death rate and liver tissue injury were observed. We also evaluated inflammation- and ferroptosis-related indices. Next, we examined the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/Glutathione Peroxidase 4 (GPX4) pathway-related molecules to elucidate the underlying mechanism.

Results: ADSC-exo reduced cell injury and Ferroptosis in VECs. ADSC-exo increased the expression and nuclear translocation of Nrf2. In the CLP-induced sepsis model, ADSC-exo relieved liver injury and reduced the death rate. Further observations showed that ADSC-exo significantly alleviated oxidative stress injury and Ferroptosis in liver tissue, while remarkably increasing the expression of Nrf2 and GPX4.

Conclusion: These findings demonstrate the remarkable ability of ADSC-exo to alleviate sepsis-induced ALI by mitigating endothelial cell Ferroptosis, providing evidence for the potential clinical application of ADSC-exo in ALI therapy.

Keywords

ADSC exosome; Acute liver injury; Nrf2; ferroptosis; sepsis.

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