Figure 5.

ESI-017 hNSCs Implanted in Q140 Mice Improve Behavior and Exhibit Evidence of Differentiation into Immature Neurons and Astrocytes

(A) Transient improvement in motor coordination (pole task) 3 months after cell injection. WT Veh (n = 20), Q140 Veh (n = 18), Q140 hNSC (n = 18). One-way ANOVA with Bonferroni post hoc test: ^∗p < 0.05, ^∗∗p < 0.01.

(B–D) Persistent improvement of running wheel deficits 5.5 months post treatment (n = 5 per group). (B) Graph showing mean running wheel rotations/3 min/night over 2 weeks, in 7.5-month-old male WT or Q140 mice 5.5 months post treatment. Comparison by two-way ANOVA: group effect F = 52.93, p < 0.0001; night in running wheel effect F = 17, p < 0.0001. Bonferroni post hoc test: ^∗p < 0.01, ^∗∗p < 0.001, and ^∗∗∗p < 0.0001 compared with Q140 Veh. (C) Total average running wheel turns at night over 2 weeks. Two-way ANOVA with Bonferroni post hoc test: ^∗p < 0.01, ^∗∗p < 0.001. (D) Slope of motor learning not significant between the three groups.

(E and F) Novel object recognition. hNSCs prevented the deficit in Q140 mice 5 months post treatment but not at 3 months in the discrimination index of sniffing time (E) or number of bouts (F). WT Veh n = 18, Q140 Veh n = 18, and Q140 hNSC n = 19. One-way ANOVA with Bonferroni post hoc test: ^∗p < 0.05, ^∗∗p < 0.01.

(G) Survival and differentiation of hNSCs in Q140 mice by staining with the human specific antibody (HNA, red; a and d) co-expressing with astrocytes (GFAP, green; b and c) or neuron-restricted progenitors (DCX, green; e and f). Scale bar, 20 μm.

All graphs show mean ± SEM.