Therapeutic potential of human mesenchymal stem cells and insulin-like growth factor-I gene therapy in animal models of neurodegeneration

MOREL GR; LOPEZ LEÓN M.; GOYA RG; ZAPPA VILLAR MF; PARDO J; MAZZOLINI G; GARCÍA MG; TRÍPODI LS; REGGIANI PC

Buenos Aires

Congreso; Young Investigators Symposia. 2nd Federation of Latin American and Caribbean Neuroscience Societies (FALAN) Congress; 2016

FALAN - IBRO

Our objective is to develop therapeutic strategies for neurodegenerative disorders, as Alzheimer´s Disease (AD), and brain aging. Gene therapy combined with the use potent neuroprotective molecules, like Insulin-like growth factor 1 (IGF-1), emerge as promising tool for this purpose. We constructed an adenoviral vector for rat IGF-1 and implemented intracerebroventricular (ICV) IGF-I restorative gene therapy in the brain of aging rats. The treatment improved the spatial memory accuracy and, in the hippocampus, increased the number of immature neurons and modified astrocytes branching and number.More recently we implemented human mesenchymal stem cell (MSC) therapy in a rat sporadic AD-model (by ICV injection of streptozotocin) as well as in aging rats. First, we explored the therapeutic effect of MSC ICV injection. In our AD rat model, ICV cell therapy improved the rat spatial and recognition memories performances. Comparable results were observed when we used a similar experimental design in aging rats. Also, in this study we found that cell therapy improves cognitive deficits. Finally, we assessed the effect of repeated intravenous administrations of MSC on cognitive performance in the AD rat model. This treatment improved memory, depression-like and anxiety-like behaviors. In sum, our results are agree with the emerging evidence that supports the use of MSCs for regenerative applications in neurodegenerative disorders and brain aging.