State of problem: Grafting of primary embryonic neural tissue has proven that cell replacement therapy is a viable approach to the treatment of PD. However, the number of successfully grafted patients is relatively small due to limited access to suitable donor tissue.
Alternative sources of donor tissue - which are reproducibly homogeneous in their cellular composition and can be generated in large quantities - are urgently needed for cell transplantation to become a widely available therapy for PD.
Overriding objective: To propagate human embryonic stem (hES) cell lines and differentiate them into dopaminergic (DA-ergic) neurons, which can be used for neural grafting in Parkinson's disease (PD).
Aims of the present project:
- To expand cells from hES cell lines established by Lund University collaborators (SAO1 (Cell Therapeutic Scandinavia AB, Goteborg, Sweden) and #237 (Karolinska Institute, Stockholm, Sweden)) and to identify epigenetic stimuli that promote their differentiation into a uniform, enriched population of DA-ergic neurons.
- To assess the DA-ergic phenotype of the hES-cell-derived neurons in vitro, regarding the expression of markers for dopamine production and handling, and exhibition of spontaneous firing as well as spontaneous and drug-induced dopamine release.
- To assess the ability of grafted hES-cell derived neurons to restore DA-ergic neurotransmission in vivo by examining their effects on behaviour in immunosuppressed hemiparkinsonian rats and their capacity to produce and release dopamine, as well as to form synapses.
Fields of science
Call for proposal
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