Presented to the AACT 2015 Conference

The efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSC) to the brain in the rat 6-hydroxydopamine model of Parkinson’s disease (PD). Our recent studies examined the delivery of bone marrow derived MSC, macrophages and microglia to the brain in transgenic models of PD ((Thy1)-h[A30P] αS), Alzheimer’s disease (APP/PS1) and in a human glioma model via intranasal application (INA). Our data show a targeted intranasal delivery of microglia in naïve BL/6 mice. In the (Thy1)-h[A30P] αS transgenic mice intranasally delivered MSC appeared predominantly within the OB and brainstem. INA of MSCs in APP/PS1 mice led to therapeutically efficacious delivery of cells to different brain regions including hippocampus and cortex. Both, macrophages and MSCs appeared at the tumor edge in an intracranial model of human glioma. We provide proof of principle for intranasal delivery of cells to the brain in transgenic PD and AD mouse models as well as in a mouse model of human glioma. Our follow-up studies will aim at novel approaches to enhance the migratory capacities of therapeutic cells and to determine the optimal dosage (single treatment regimen or repeated administrations) to achieve the long-term functional improvement in these models of brain disorders.