Journal: Frontiers in Pharmacology
Article Title: Harnessing human immune system models to validate NADPH oxidase 1 inhibition as treatment for hepatocellular carcinoma
doi: 10.3389/fphar.2026.1808515
Figure Lengend Snippet: NOX1i in Myeloid-HIS-HCC mice reduces monocyte and tumor-associated macrophage infiltration. (A) Schematic overview of the experimental set-up. Male NSG-SGM3 mice (n = 11) were sublethally irradiated and the immune system was partly reconstituted using human cord blood (CB)-derived hematopoietic stem and progenitor cells (HSPCs). Four weeks post humanization, orthotopic human HCC was induced and mice were treated with 50 µM ML171 (NOX1i; n = 6) or vehicle (n = 5), twice per week for 3 weeks. (B) Human-to-murine immune cell (CD45) chimerism in the indicated tissues. (C) Human engraftment based on the number of human CD45 cells. Data are represented as violin plots showing median and quartiles. (D,E) Human immune cell subsets (D) and monocyte subsets (E) in indicated tissues represented as percentage of human CD45 cells. (F) Number of human macrophages and monocytes in the indicated tissues. (G) Representative immunohistochemistry images of infiltrated human monocytes/macrophages in liver tissue of HCC-bearing humanized mice. Sections were stained for human CD14 (brown), or matched IgG control. Scale bars: 100 µm. (B,D,E) . Data are shown as mean (SD). (C–E) Adjusted p-values were calculated using multiple unpaired t-test with Holm-Šídák correction (D,E) , or p-values were calculated using unpaired t-test with Welch’s correction or unpaired Mann-Whitney U test based on normal distribution (C,E) . *p < 0.05. HCC: hepatocellular carcinoma, NOX1i: NOX1 inhibition, huCD45: human CD45, muCD45: murine CD45, NK = natural killer, DCs: dendritic cells.
Article Snippet: Freshly isolated CB-derived PBMCs, isolated from CB as described for buffy coat, were enriched for HSPCs based on positive immunomagnetic selection of CD34 + expressing cells using the human CD34 MicroBead Kit UltraPure (Miltenyi Biotec, #130–100-453) according to manufacturer’s guidelines.
Techniques: Irradiation, Derivative Assay, Immunohistochemistry, Staining, Control, MANN-WHITNEY, Inhibition