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Fig.1 Identification and characterization of human umbilical cord-derived mesenchymal stem cells and their-derived exosomes A: flow cytometry detection of MSC surface markers: HUMSCs exhibit high expression of CD29, CD44, CD90, and CD105, while low expression of CD34, CD45, and HLA-DR. B: morphology and multipotential differentiation potential of live HUMSCs (left: uninduced HUMSCs exhibit spindle and fibroblast-like morphological characteristics, 10×; middle: oil red O staining indicates adipogenic differentiation; right: Alcian blue staining indicates osteogenic differentiation). All data are from three independent experiments. C: Characterization and identification of stem cell-derived exosomes: nanoparticle tracking analysis (NTA): determination of exosome particle size distribution (50-200 nm) and concentration. Western blotting (WB): detection of exosome surface markers (CD9, CD63, CD81) and intracellular protein TSG101, with negative marker calnexin not detected, confirming exosome purity. Transmission electron microscopy (TEM): negative staining reveals a typical bilayer membrane structure and cup-like morphology.

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Fig.2 Both low-dose and high-dose exosome treatments exhibited significant therapeutic effects

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Fig.3 Detection of hepatocyte injury markers in homogenates of HL-7702 cells in each group ($\bar x \pm s $, n=3) ns: P>0.05, *: P<0.05, **: P<0.01, ***: P<0.001.

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Fig.4 Metabolomic PCA and OPLS-DA analysis A: 3D-PCA score plot of mass spectrometry data from each group. mode_c: CCl4 model group; exo: CCl4+exosome intervention group; QC: quality control group (mixed solution from each group); the same below PC1 represents the first principal component, PC2 represents the second principal component, and the percentage indicates the explanatory power of that principal component to the dataset; each point in the figure represents a sample, and samples from the same group are represented by the same color. B: grouped 2D-PCA analysis plot. C: grouped 3D-PCA analysis plot. D: OPLS-DA score plot. The abscissa represents the predictive principal component, and the direction of the abscissa indicates the differences between groups; the ordinate represents the orthogonal principal component, and the direction of the ordinate indicates the differences within groups; the percentage indicates the explanatory power of that component to the dataset.

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Fig.5 Clustering and KEGG enrichment of differential metabolites in the CCl4 group and CCl4+exosome group A: VIP value plot of differential metabolites. The x-axis represents the VIP value, and the y-axis represents metabolites. Red represents upregulated differential metabolites, and green represents downregulated differential metabolites. B: Heatmap of differential metabolite clustering. The horizontal axis represents sample names, and the vertical axis represents metabolite information. Scale represents the expression level after normalization (the redder the color, the higher the expression level; the greener the color, the lower the expression level). Group represents the grouping, and Class represents the substance classification. C: KEGG enrichment plot of differential metabolites. The x-axis represents the Rich factor corresponding to each pathway, and the y-axis represents the pathway name. The color of the points represents the P-value, with red indicating more significant enrichment. The size of the points represents the number of differential metabolites enriched.

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Fig.6 Cellular colocalization of exosomes with mitochondria and protective effects of exosomes on mitochondrial ultrastructure A: three-color fluorescence colocalization analysis. Blue: cell nucleus (DAPI staining); green: mitochondria (MitoTracker labeling); red: DiR or DiR-labeled exosomes. TD: bright-field observation. In the DiR+ exosome group, the overlap of red and green signals produces an orange-yellow signal, and 3D fluorescence imaging confirms the spatial colocalization of the red signal (DiR+ exosomes) and the mitochondrial marker within the cell. B: transmission electron microscopy (TEM) observation of mitochondrial ultrastructure. The CCl4 group shows disruption of the mitochondrial cristae structure, while partial structural restoration is observed in the CCl4+ exosome group.