Fig. 5: APOs@^atRANBP_miR-124-eMSCs survived and differentiated into neurons in vivo.

a Representative images of HE staining in the hippocampus after transplantation of MSCs and different eMSCs. The sham operation group without cell injection was used as the control group. b Immunofluorescent detection for Iba-1 (red) and CD45 (green) to label microglia and leukocytes in brain, respectively. The PBS-treated AD group without cell injection was used as control. c Illustration of detection of MSC-derived cells from brain tissue collection³⁰. d Quantitative analysis of MSCs and different eMSCs in brain. e Illustration of detection of MSC-derived cells in the brain slices. MSC-derived cells were localized through HNA-positive regions. The immunofluorescence image on the right is derived from the black dashed box region³¹. f Immunostaining of brain slices for neural-specific markers Tuj1 (green) and MAP2 (green) and glial-specific marker GFAP (bright blue) after implantation of MSCs and different eMSCs (HNA + , pink) for 30 days, respectively. White dotted lines indicate the graft. g Quantification of fluorescence signal of MAP2, Tuj1, and GFAP. h Morphology of transplanted PBS-^PKH-26MSCs (yellow) and APOs@^atRANBP_miR-124-^PKH-26eMSCs (yellow) in brains of APP/PS1 mice 30 days post-transplantation, respectively. The white dashed box indicates the magnified region. i Representative voltage-dependent membrane currents of PBS-^PKH-26MSCs and APOs@^atRANBP_miR-124-^PKH-26eMSCs in the brain slices. j Representative fluorescence images showing the position of transplanted APOs@^atRANBP_miR-124-^PKH-26eMSCs (yellow) in the brains of APP/PS1 mice at 3 days and 30 days post-transplantation, respectively. The white dashed box indicates the magnified region and the white arrows indicate PKH-26 positive cells. k Immunostaining of brain slices for presynaptic marker GAP43 (red) and the postsynaptic marker PSD95 (green) after transplantation of APOs@^atRANBP_miR-124-^PKH-26eMSCs (yellow) for 30 days, respectively. The solid white wire boxes indicate the magnified regions and the white arrow refers to the synapse formation between transplanted eMSCs with host cells. Data were presented as mean ± SD (n = 3 mice in d; n = 5 mice in g). One-way ANOVA with Tukey post-hoc test was used for statistical analysis of d, g. Three independent experiments were performed with similar results and representative results are shown (a, b, h, j, k). Source data are provided as a Source Data file.