Silvia Bolognin, Marie Fossépré, Xiaobing Qing, Javier Jarazo, Janez Ščančar, Edinson Lucumi Moreno, Sarah L Nickels, Kobi Wasner, Nassima Ouzren, Jonas Walter, Anne Grünewald, Enrico Glaab, Luis Salamanca, Ronan M T Fleming, Paul M A Antony, Jens C Schwamborn
Parkinson's disease (PD)-specific neurons, grown in standard 2D cultures, typically only display weak endophenotypes. The cultivation of PD patient-specific neurons, derived from induced pluripotent stem cells carrying the LRRK2-G2019S mutation, is optimized in 3D microfluidics. The automated image analysis algorithms are implemented to enable pharmacophenomics in disease-relevant conditions. In contrast to 2D cultures, this 3D approach reveals robust endophenotypes. High-content imaging data show decreased dopaminergic differentiation and branching complexity, altered mitochondrial morphology, and increased cell death in LRRK2-G2019S neurons compared to isogenic lines without using stressor agents...
January 9, 2019: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)