A new brain organoid model to study Parkinson’s Disease

in Biomedical Science and Engineering (2021)

Monitoring the neurotransmitter release of human midbrain organoids using a redox cycling microsensor as a novel tool for personalized Parkinson’s disease modeling and drug screening.

in Analyst (2021)

Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids

in Cell and Tissue Research (2020)

Midbrain organoids: A new tool to investigate Parkinson's disease

in Frontiers in Cell and Developmental Biology (2020)

Generation of midbrain organoids as a model to study Parkinson's disease

Doctoral thesis (2019)

The study of 3D cell culture models not only bridges the gap between traditional 2D in vitro experiments and in vivo animal models, it also addresses processes that cannot be recapitulated by these ... [more ▼]

The study of 3D cell culture models not only bridges the gap between traditional 2D in vitro experiments and in vivo animal models, it also addresses processes that cannot be recapitulated by these traditional models. Therefore, it offers an opportunity to better understand complex biology, for instance brain development, where conventional models have not proven successful. The so{called brain organoid technology provides a physiologically relevant context, which holds great potential for its application in modelling neurological diseases. To obtain these highly specialised structures, resembling specifically key features of the human midbrain, we derived a human midbrain-specific organoid (hMO) system from regionally patterned neural stem cells (NSCs). The resulting neural tissue exhibited abundant neurons with midbrain dopaminergic neuron (mDAN) identity, as well as astroglia and oligodendrocyte di erentiation. Within the hMOs, we could observe neurite myelination and the formation of synaptic connections. Regular fire patterning and neural network synchronicity were determined by multielectrode array (MEA) recordings. In addition to electrophysiologically functional mDANs producing and secreting dopamine (DA), we also detected responsive neuronal subtypes, like GABAergic and glutamatergic neurons. To investigate Parkinson's disease (PD)-relevant pathomechanisms, we derived hMOs from PD patients carrying the LRRK2-G2019S mutation and compared them to healthy control hMOs. In addition to a reduced number and complexity of mDANs, we determined a signi cant increase of the stem cell marker FOXA2 in the patient-derived hMOs. This suggests a neurodevelopmental defect induced by a PD-specific mutation and emphasises the importance of advanced three-dimensional (3D) stem cell-based in vitro models. The in this thesis described hMOs are suitable to reveal PD{relevant phenotypes, thus constitute as a powerful tool for human-specific in vitro disease modelling of neurological disorders with a great potential to be utilised in advanced therapy development. [less ▲]

Modeling Parkinson’s disease in midbrain-like organoids

in NPJ Parkinson's Disease (2019)

In vivo Phenotyping of Human Parkinson’s Disease-Specific Stem Cells Carrying the LRRK2-G2019S Mutation Reveals Increased a-Synuclein Levels but Absence of Spreading

in Opera Medica et Physiologica (2018)

Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells

in Stem Cell Reports (2017)