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. 2014 Jun 26;3(2):242–249. doi: 10.1016/j.stemcr.2014.05.017

Figure 2.

Figure 2

hiPSC-GRNPs Transplantation Improved Motor Score and Survival in ALS Model Mice

(A) Transplantation schedule and schema of spinal cord injection site. Transplantation was performed after disease onset.

(B) Mice presented with no side effects after transplantation and made vigorous twisting movements with hind-limb extension, as shown by representative photos at tail suspension. Both groups showed no change in motor clinical score at 24 hr after surgical insult.

(C) Clinical motor scoring change by sequential evaluation showed significant difference from 100 to 120 days after birth (∗p < 0.05). Data represent mean ± SEM (n = 21 mice per group).

(D) Lifespan was prolonged in the hiPSC-GRNPs transplantation group (162.2 ± 12.8 days) compared to the control group (150.4 ± 12.1 days) (∗∗p < 0.01). Data represent mean ± SD (n = 21 mice per group).

(E) Survival (Kaplan-Meier plot) analysis shows a significant difference between the PBS injection group survival (black line) and the hiPSC-GRNPs transplantation group survival (green line) throughout the course of the study (n = 21 mice per group, p = 0.00691 stratified log-rank test), suggesting that the hiPSC-GRNPs transplantation group had better survival (∗∗p < 0.01).

(F) The number of axons in L4 ventral nerve root was counted to estimate surviving motor neurons at the middle stage of disease progression. At 120 days after birth, transverse sections of ventral nerve roots were stained with an anti-neurofilament-H antibody. Compared to littermates without transgene, the number of axons in Tg SOD1-G93A mice was decreased. Each axon caliber was measured and classified according to size.

(G) Cumulative axon caliber distribution at L4 ventral root at 120 days after birth of both groups. Two-way ANOVA with repeated-measures was used to study the effect of transplantation (transplanted and nontransplanted mice) on axonal caliber distribution. Pairwise comparisons were made using Bonferroni adjustment (∗p < 0.05). The number of 1–2 μm caliber axons was significantly decreased and the number of 6–8 μm caliber axons was significantly increased in the hiPSC-GRNPs transplantation group. Data represent mean ± SD (n = 3 mice per group).

Scale bars, 100 μm. hiPSCs, human induced pluripotent stem cells; hiPSC-GRNPs, hiPSC-derived glial-rich neural progenitors. See also Figure S1 and Table S1.