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Content archived on 2024-05-29

Dopaminergic neurons from human embryonic stem cell grafted in models of Parkinson's disease


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.

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Paradisgatan 5C

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