[The molecular mechanism of metformin-adipose mesenchymal stem cell derived exosome complex in regulating macrophage polarization to ameliorate liver ischemia-reperfusion injury].

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objective This study aimed to investigate the protective effect of a metformin (Met)-adipose-derived mesenchymal stem cell exosome (ADSC-Exo) complex (Met-Exo) against hepatic ischemia-reperfusion injury (IRI) and to determine whether this protection is mediated through the silent information regulator 1(SIRT1)-tissue inhibitor of metalloproteinase 3(TIMP3) axis. Methods Met-Exo was constructed and characterized by nanoparticle tracking analysis, Western blotting, and transmission electron microscopy (TEM). An in vitro model of hepatic IRI was established in mouse hepatocyte AML12 cells subjected to oxygen-glucose deprivation/re-oxygenation (OGD/R). Cell viability, apoptosis, and hepatocyte function markers (AST and ALT) were measured to compare the protective effects of Met-Exo, ADSC-Exo, and Met alone. A Transwell TM co-culture system was used to evaluate how macrophage polarization influences OGD/R-induced AML12 injury. AML12 cells were assigned to the following groups: Ctrl, OGD/R, Met, ADSC-Exo, Met-Exo, and macrophage-polarization groups (M0, M1, M1+Met-Exo, M1+pcDNA3.1, M1+pcDNA3.1-SIRT1, M1+pcDNA3.1-TIMP3). SIRT1 and TIMP3 protein levels in AML12 cells were determined by Western blot. Macrophage-polarization markers-inducible nitric-oxide synthase (iNOS) and arginase 1 (Arg1) were also quantified. In parallel, AML12 cells' viability, apoptosis, and hepatocellular functi

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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