Stem cell based generation of midbrain dopaminergic neurons. Towards cellular tools to study Parkinson’s disease

PhD ceremony: Mr. R.A. Roessler, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Stem cell based generation of midbrain dopaminergic neurons. Towards cellular tools to study Parkinson’s disease

Promotor(s): prof. H.W.G.M. Boddeke

Faculty: Medical Sciences

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders worldwide. It affects around 2% of the population older then 60 years and to date no cure is available. A important symptom of PD is the selective loss of a specific type of neurons in the brain, called dopaminergic (DA) neurons. These neurons undergo cell death in a confined area of the brain and deterioration of their neural connections results in classical symptoms of PD, such as tremor, rigidity, bradykinesia, depression and mental retardation. More than two decades ago cell replacement strategies utilizing embryonic tissue were considered as therapeutic tool, but technical and ethical obstacles could not be overcome. Now, stem cells and in particular induced pluripotent stem cells (iPSCs) have the potency and provide promise to solve those issues. In this thesis several stem cell types have been generated and analyzed regarding their suitability to serve as tool to study or treat PD. Latest discoveries in the field of regenerative medicine have put iPSCs in the center of attention for potential cell replacement approaches. Particularly human iPSC, which are artificially generated patient-specific stem cells, allow the generation of individually tailored iPSC-derived DA neurons and therefore leap issues such as lack of immune-compatibility, ethical concerns and lack of sufficient modeling capacity. This thesis describes the successful generation of patient-specific DA neurons derived from iPSCs. Moreover, we provide an extensive comparative characterization and functional analysis of mouse iPSC-derived DA neurons, which will serve as model system to study PD.