Fig. 6: SIRP-EV outperforms C-EV in ALF models, attributed to SIRPα expression.

A Representative histological images of H&E and TUNEL in liver tissue from normal and APAP-ALF mice after EVs treatment. B Quantification of TUNEL-positive cells. Box graph data are presented as mean ± SD. Box plot minima = 0, 0, 2, 1; maxima = 49, 332, 200, 58; center = 1, 28.5, 38.5, 6. C Flow cytometry determination of Ly6Chigh as a percentage of total liver CD11bhigh F4/80low MoMFs (n = 4 for Normal and APAP groups, and n = 5 for APAP + C-EV and APAP + SIRP-EV groups). D Serum AST (n = 7 for Normal and APAP + SIRP-EV groups, n = 8 for APAP group, and n = 9 for APAP + C-EV groups) and ALT (n = 8 for Normal, APAP + C-EV, and APAP + SIRP-EV groups, n = 9 for APAP group) levels were measured 48 h post-500 mg/kg APAP induction in subjects treated with 4 × 109 EVs. E Representative IHC images of α-SMA staining in liver tissues from mice that survived 120 h after induction with a 700 mg/kg dose of APAP. Quantification of α-SMA is shown in the right panel. Box represents the distribution of combined sample results across independent experiments. Box graph data are presented as mean ± SD. Box plot minima = 0.189, 0.884, 0.061; maxima = 9.321, 7.306, 4.731; center = 2,696, 2.406, 0.725. F–I Therapeutic effects of 9 × 108 EVs on an LPS/d-galN-induced ALF model. F Representative histological images of H&E and TUNEL staining in liver tissue from normal and LPS/d-galN-induced ALF mice after the indicated treatment. G Quantification of the TUNEL-positive area (n = 5 for PBS group, n = 10 for Normal, C-EV, and SIRP-EV groups). H Serum ALT levels were determined 8 h post-LPS/d-galN injection (n = 7 for PBS, C-EV, and SIRP-EV groups, n = 8 for the Normal group). I Kaplan–Meier survival curves for LPS/d-galN-induced ALF mice treated with EVs (n = 16 for LPS/d-galN group, n = 18 for LPS/d-galN+C-EV group, and n = 19 for LPS/d-galN+SIRP-EV group, across three independent experiments). J–L Therapeutic efficacy of 5 × 108 EVs in TAA-induced ALF models. J Representative histological images of H&E, TUNEL, and CD47 staining in liver tissue from both normal and TAA-induced ALF mice following EVs treatment. K Quantification of TUNEL-positive cells in liver tissue. Box graph data are presented as mean ± SD. Box plot minima = 0, 107, 150.8, 5; maxima = 11.6, 533.7, 429.3, 136; center = 0, 232.1, 284.3, 46.5. L Serum ALT (n = 5 per group) and total bilirubin (n = 6 per group) levels were determined 40 h post-TAA injection. Bar graph data are presented as mean ± SD. Statistical significance was determined by one-way ANOVA with Tukey’s post hoc test (B–E, G, H, K, L). Source data are provided as a Source Data file.