Adipose-derived Mesenchymal Stem Cells-Derived Exosomes Alleviate LPS-Induced Hepatocyte Injury in Sepsis by Inhibiting the JAK2/STAT3 Signaling Pathway

The severity of sepsis-induced hepatic injury severely impacts disease progression and prognosis. Hence, this study investigates the role of adipose-derived mesenchymal stem cells (ADSCs)-derived exosomes (ADSCs-exo) in mitigating hepatic injury during sepsis. An in vitro model of sepsis-induced hepatic injury was established by stimulating HepG2 cells with lipopolysaccharide (LPS). ADSCs were either co-cultured with LPS-injured HepG2 cells or used to isolate exosomes for subsequent treatment. The characteristics of ADSCs-derived exosomes were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. ADSCs-exo uptake by hepatocytes was assessed via PKH67 labeling. Cell viability, apoptosis, and lactate dehydrogenase (LDH) release were evaluated using Cell Counting Kit-8, flow cytometry, and commercial assays, respectively. The involvement of the janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was further investigated. Both ADSCs and ADSCs-exo notably attenuated LPS-induced hepatocyte injury, as evidenced by lowered LDH release, enhanced cell viability, and suppressed apoptosis. ADSCs-exo were internalized by HepG2 cells. Treatment with ADSCs-exo led to a notable downregulation of phosphorylated JAK2 and STAT3. Moreover, pharmacological activation of the JAK2/STAT3 pathway partially reversed the protective effects of ADSCs-exo. Collectively, ADSCs-exo alleviate LPS-induced hepatocyte injury by inhibiting activation of the JAK2/STAT3 signaling pathway. These findings underscore the potential of ADSCs-exo as a promising cell-free therapeutic strategy for sepsis-associated liver injury.