Fig. 6: Cre recombination in R26-LSL-tdTomato reporter mice by VEDIC and VFIC engineered EVs after local (ICV or osmotic pump ICV) and systemic (IP) injections.

a Workflow for the intracerebroventricular (ICV) injection of engineered EVs to deliver Cre in CNS of R26-LSL-tdTomato reporter mice. b TdTomato expression analyzed by immunofluorescence in different regions of CNS after ICV injection of engineered EVs. Scale bar, 50 µm for cerebellum and cortex, and 200 µm for hippocampus. c Workflow for the osmotic pump ICV injection of engineered EVs to transfer Cre to CNS in R26-LSL-tdTomato reporter mice. d Percentage of tdTomato+ cells in the brain tissues after osmotic pump ICV injection of engineered EVs quantified by flow cytometry, analyzed 4 days after the infusion. n = 4 mice for PBS group and n = 5 mice for other groups. e Schematic workflow for the intraperitoneal (IP) injection of engineered EVs into R26-LSL-tdTomato reporter mice. f TdTomato expression in liver and spleen after IP injection of engineered EVs, analyzed one-week post injection. Scale bar, 50 µm. g Co-staining of tdTomato and the T cell marker CD3 in spleen as detected by immunofluorescence one week after IP injection of engineered EVs. Scale bar, 50 µm. h Co-staining of tdTomato and the B cell marker B220 in spleen one week after IP injection of engineered EVs. Scale bar, 50 µm. i Co-staining of tdTomato and the macrophage marker F4/80 in spleen one week after IP injection of engineered EVs. Scale bar, 50 µm. n = 3 mice per group, representative images for (b) and (f–i). Two-way ANOVA (Tukey) multiple comparisons test was used for analysis of (d). Data are shown as mean ± SD. c Created in BioRender.com, Zheng, W. (2025) https://BioRender.com/z93x284. Exact statistical analysis was reported in the Source data and Source data are provided as a Source Data file.