FORNEUROCELL II

BAVARIAN RESEARCH ASSOCIATION FOR ADULT NEURONAL STEM CELLS

Non-invasive detection of functional integration of optically-controlled stem cells by (f)MRI in vivo

Various adult stem cell populations are currently being evaluated regarding their restorative potential in the experimental therapy of degenerative CNS disorders. However, the key question whether this effect is mediated by restoring network function remains open up to now. In previous studies we were able to visualize transplanted stem cells by high resolution MRI in vivo, by labeling the cells with iron-oxide nanoparticles (VSOP). In the current study, we aim for a combined imaging approach to test for functional integration of newborn stem-cell derived neurons into host circuitry upon transplantation. To achieve this goal, we transduce adult stem cells provided by the ForNeuroCell network in vitro with the light activated cation channel Channelrhodopsin in combination with a bioluminescent reporter gene, enabling temporally precise and specific optical control of membrane potential, and in the case of stem-cell derived neurons, action potential generation. We will evaluate the properties of adult stem-cells provided by our collaborators within the ForNeuroCell network, to integrate into local host circuitry by stimulating transplanted ChR2-expressing stem cells using an optical fiber in vivo, thereby selectively inducing neuronal firing of adult stem cell derived neurons. We will use functional MRI to test for specific effects of exogenous cells on network activity, in combination with morphological MRI and bioluminescence imaging, assessing localization and differentiation stage.