Extracellular vesicles from adipose-derived mesenchymal stem cells alleviate acute lung injury via the CBL/AMPK signaling pathway.

in BMC biology by Yan Xiong, Lulu Wang, Bohao Li, Beibei Fu, Zhou Sha, Jin Liu, Rong Tian, Rui Yao, Feng Lin, Zixuan Cong, Yongliang Du, Xiaoyuan Lin, Haibo Wu

TLDR

  • The study found that adipose-derived mesenchymal stem cells (ADSCs)-derived extracellular vesicles (EVs) can alleviate acute lung injury (ALI) by modulating metabolic processes through the CBL/AMPK signaling pathway.
  • ADSCs-derived EVs improved lung injury, restored mitochondrial function, and inhibited inflammation and apoptosis in ALI mice.
  • This highlights the potential therapeutic application of ADSC-derived EVs in mitigating ALI and further research is needed to explore its mechanisms and optimal administration protocols.

Abstract

Acute lung injury (ALI) which is caused by Staphylococcus aureus (SA), is a serious lung disease that threatens human health. Although some current treatments are effective in alleviating ALI, they still have a significant mortality rate. At present, adipose-derived mesenchymal stem cells (ADSCs)-derived extracellular vesicles (EVs) have been investigated for the treatment of various diseases. Here, we examined the role of ADSCs-derived EVs in regulating apoptosis and inflammation during ALI. We showed that ADSCs and ADSCs-derived EVs supplementation could improve lung injury, restore mitochondrial function, and inhibit inflammation and apoptosis in ALI mice. Furthermore, miR-320a was present in EVs derived from ADSCs, and it can be transferred into lung tissue. In vitro, Casitas B-lineage lymphoma (CBL) expression was inhibited by miR-320a mimics. Finally, we found that miR-320a alleviated mitochondrial damage, inflammation, and apoptosis via the CBL/AMPK/JNK pathway. In conclusion, EVs from ADSCs could alleviate ALI via the CBL/AMPK signaling pathway. Therefore, the purpose of our study was to investigate the application of ADSC-derived EVs in mitigating ALI by modulating metabolic processes.

Overview

  • The study investigated the role of adipose-derived mesenchymal stem cells (ADSCs)-derived extracellular vesicles (EVs) in regulating apoptosis and inflammation during acute lung injury (ALI) caused by Staphylococcus aureus (SA).
  • The purpose of the study was to evaluate the potential of ADSC-derived EVs in mitigating ALI by modulating metabolic processes.
  • The researchers examined the effects of ADSCs and ADSCs-derived EVs supplementation on lung injury, mitochondrial function, inflammation, and apoptosis in ALI mice.

Comparative Analysis & Findings

  • The study showed that ADSCs and ADSCs-derived EVs supplementation improved lung injury, restored mitochondrial function, and inhibited inflammation and apoptosis in ALI mice.
  • ADSCs-derived EVs contained miR-320a, which can be transferred into lung tissue and modulate metabolic processes.
  • The CBL/AMPK/JNK pathway was found to be involved in the alleviation of ALI by ADSC-derived EVs, as indicated by the inhibition of CBL expression and the alleviation of mitochondrial damage, inflammation, and apoptosis.

Implications and Future Directions

  • The study highlights the potential therapeutic application of ADSC-derived EVs in mitigating ALI, especially in combination with modulation of the CBL/AMPK signaling pathway.
  • Future studies should investigate the optimal dose, route, and timing of administration of ADSC-derived EVs, as well as their potential synergistic effects with other therapies.
  • Additionally, further research is needed to explore the potential mechanisms underlying the effects of ADSC-derived EVs on ALI and to identify potential biomarkers for therapeutic efficacy.
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