Abstract

3D Cultures to Study Parkinson’s Disease

Silvia Bolognin, Research Scientist, University of Luxembourg

Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting the aging population. Despite tremendous research efforts in the course of more than a century, the cause of the disease is still unknown. Our lab focuses on the optimization of advanced human in vitro models to understand the molecular basis underlying PD. We have established the cultivation of PD patient-specific neurons, derived from induced pluripotent stem cells carrying the LRRK2-G2019S mutation, in 3D microfluidics. In contrast to conventional 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 controls without using stressor agents. Pushing forward the optimization of a model recapitulating the human brain tissue, the cultivation of midbrain brain organoids was also established in microfluidic devices. PD organoids show fewer dopaminergic neurons compared to organoids derived from healthy subjects. These data support the use of 3D models to study complex cellular mechanisms underlying PD and allow for testing the effect of disease-modifying compounds using human-derived material.