A Mesenchymal Stem Cell Line Transplantation Improves Neurological Function and Angiogenesis in Intraventricular Amyloid β-Infused Rats

Background: Mesenchymal stem cell transplantation is demonstrated to improve neurological performance in neurodegenerative diseases including Alzheimer's disease. Objective: The objective of this study is to understand the underlying mechanism of such improvement. Methods: Amyloid β (Aβ) peptide was infused into the lateral ventricle of adult Wister rats using the osmotic pump. After 15 days of continuous infusion, a mesenchymal stem cell line (B10) was transplanted in the lateral ventricle. Learning-related behavior was evaluated by 2-way shuttle avoidance test. Fifteen days after B10 transplantation, pathological and expressional changes were evaluated. Results: Compared to sham group, learning-related behavior was significantly decreased in Aβ-infused non-transplanted group, but not in B10-transplanted group. Nissl staining results demonstrated that the number of hippocampal pyramidal neurons in CA1 area in B10-transplanted group was similar to the sham group, whereas that was decreased in Aβ-infused non-transplanted group. Aβ mainly deposited in the vessels of the brains of Aβ-infused non-transplanted rats, which was decreased by B10 transplantation. Moreover, B10 transplantation increased vessel density as well as endoglin positive cells. The number of astrocyte and microglia was decreased in Aβ-infused non-transplanted group, which was returned to the level of sham animals by B10 transplantation. Real-time PCR and immunostaining results showed that B10 transplantation significantly increased IL-1β mRNA and protein expression. Conclusion: Thus, our result showed that MSC transplantation effectively decreased Aβ deposition in the cerebral vessel and increased angiogenesis, which could be a possible cause of improved neurological performance in Aβ-infused AD model rats.