Details

Autor(en) / Beteiligte

• Zanetti, Cristian
• Spitz, Sarah
• Berger, Emanuel
• Bolognin, Silvia
• Smits, Lisa M
• Crepaz, Philipp
• Rothbauer, Mario
• Rosser, Julie M
• Marchetti-Deschmann, Martina
• Schwamborn, Jens C
• Ertl, Peter

Titel

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

Ist Teil von

• Analyst (London), 2021-04, Vol.146 (7), p.2358-2367

Ort / Verlag

England: Royal Society of Chemistry

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• In this study, we have aimed at developing a novel electrochemical sensing approach capable of detecting dopamine, the main biomarker in Parkinson's disease, within the highly complex cell culture matrix of human midbrain organoids in a non-invasive and label-free manner. With its ability to generate organotypic structures in vitro , induced pluripotent stem cell technology has provided the basis for the development of advanced patient-derived disease models. These include models of the human midbrain, the affected region in the neurodegenerative disorder Parkinson's disease. Up to now, however, the analysis of so-called human midbrain organoids has relied on time-consuming and invasive strategies, incapable of monitoring organoid development. Using a redox-cycling approach in combination with a 3-mercaptopropionic acid self-assembled monolayer modification enabled the increase of sensor selectivity and sensitivity towards dopamine, while simultaneously reducing matrix-mediated interferences. In this work, we demonstrate the ability to detect and monitor even small differences in dopamine release between healthy and Parkinson`s disease-specific midbrain organoids over prolonged cultivation periods, which was additionally verified using liquid chromatography-multiple reaction monitoring mass spectrometry. Furthermore, the detection of a phenotypic rescue in midbrain organoids carrying a pathogenic mutation in leucine-rich repeat kinase 2, upon treatment with the leucine-rich repeat kinase 2 inhibitor II underlines the practical implementability of our sensing approach for drug screening applications as well as personalized disease modelling. A novel dopamine targeted electrochemical detection strategy has enabled the phenotyping and non-invasive monitoring of human midbrain organoids (healthy and Parkinson's diseased), by employing a redox-cycling based microsensor.