WP6: Directed fibre outgrowth of neuronal cells

Our brain consists of a network of more than 86 billion nerve cells that carry two types of protrusions (or fibres) named axons and dendrites: Axons are able send electrical signals from the cell body all along the thin fibres to the distal end where the signal is transmitted via synaptic switch points to the next nerve cell`s  dendrite. Neurons carry trees of dendrites allowing to receive and to compute thousands of synaptic inputs resulting in the modulation of the firing rate of the outgoing single axon to the subsequent connecting nerve cell.

In Parkinson`s disease certain types of nerve cells permanently degenerate and thus disconnect themselves form their field of target innervation. As in the adult human brain neurons cannot be replaced there is an emerging concept to transplant cultured neurons producing the neurotransmitter dopamine. We generate such dopamine releasing neurons in cultures derived from human stem cells.

Unfortunately, it is general knowledge that after transplantation into the brain, axons arising from the neurons do not know where to grow but need guidance. Our idea is to enhance the regeneration capacity of the transplanted stem cell derived neurons by activating the nerve cell´s own inside regeneration machinery using nanoparticles with tailored functions.

Using an external magnet in the space mode we move the intracellular nanoparticles to the tip off their growing fibres. The final aim is to guide the growing axon of the transplanted human nerve cell into the disconnected brain region thereby repairing the previously disturbed connectivity.