Mesenchymal Stem Cells Increase Hippocampal Neurogenesis and Neuronal Differentiation by Enhancing the Wnt Signaling Pathway in an Alzheimer's Disease Model

Neurogenesis in the subgranular zone of the hippocampal dentate gyms may act as an endogenous repair mechanism in Alzheimer's disease (AD), and the Wnt signaling pathway has been suggested to closely modulate neurogenesis in amyloid-beta (A beta)-related AD models. The present study investigated whether mesenchymal stem cells (MSCs) would modulate hippocampal neurogenesis via modulation of the Wnt signaling pathway in a model of AD. In A beta-treated neuronal progenitor cells (NPCs), the cocukure with MSCs increased significantly the expression of Ki-67, GFAP, SOX2, nestin, and HuD compared to A beta treatment alone. In addition, MSC treatment in A beta-treated NPCs enhanced the expression of beta-catenin and Ngn1 compared to A beta treatment alone. MSC treatment in A beta-treated animals significantly increased the number of BrdU-ir cells in the hippocampus at 2 and 4 weeks compared to A beta treatment alone. In addition, quantitative analysis showed that the number of BrdU and HuD double-positive cells in the dentate gyms was significantly higher in the MSC-treated group than in controls or after A beta treatment alone. These results demonstrate that MSC administration significantly augments hippocampal neurogenesis and enhances the differentiation of NPCs into mature neurons in AD models by augmenting the Wnt signaling pathway. The use of MSCs to modulate endogenous adult neurogenesis may have a significant impact on future strategies for AD treatment.