Assessment of the Role of NOGO Gene Block in Enhancing the Neuro-regenerative Effect of Mesenchymal Stem Cells.

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Abstract Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal disease. Mesenchymal stem cells (MSCs) have a therapeutic potential in neuronal diseases, factors as NOGO-A limit axonal regeneration. In this study, gene silencing was used to suppress Nogo-A expression in MSCs to enhance its neuro-regenerative role. Methods: mouse models of motor neuron degeneration were created, effect of non-modified and plasmid transfected MSCs were studied clinically and histologically. Group 1 received no treatment. Group 2 received IV injection of non modified MSCs and sacrificed after 8 days (subgroup 2a) and 15 days (subgroup 2b) following treatment, Group 3 received IV injection of transfected MSCs and were sacrificed after 8 days (subgroup 3a) and 15 days (subgroup 3b) following treatment. Results: A significant increase in weight and motor scores of subgroups 2a & 2b occurred in comparison to subgroups1a & 1b respectively (p values <0.001, <0.001, 0.001 & 0.026 respectively), GAP43 expression in group 2 mice was significantly higher compared to group 1 mice (p value <0.001). Deformed neurons and glial cells in group 2 were significantly lower compared to group 1 mice (p value <0.001). Deformed neurons and glial cells in subgroup 2b were significantly less in comparison to subgroup 2a (p values = 0.002 and 0.03) indicating an improvement with time. GAP43 in subgroup 2b was significantly higher compared to subgroup 2a (p value = 0.030).Weight and motor power in group 3 mice was significantly higher when compared to group 1 on days; 14 and 21 (p values <0.001, <0.001, <0.001 and 0.008) respectively. Deformed neurons and glial cells in group 3 mice were significantly lower when compared to group 1 mice (p values <0.001). GAP43 expression in group 3 mice was significantly higher when compared to group1 (p value <0.001). Deformed neurons in subgroup 3b was significantly less than subgroup 3a (p value <0.001). GAP43 expression in group 3 mice was significantly increased when compared to group 2 mice (p value <0.001).Conclusion: NOGO-A gene SiRNA is a potential enhancer of the neuro-regenerative action of MSCs.

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