Resources
Authors & Affiliations
Anna Kocsis, Judit P. Vigh, Ana R. Santa-Maria, Nóra Kucsápszky, Silvia Bolognin, Jens C. Schwamborn, András Kincses, Anikó Szecskó, Szilvia Veszelka, Mária Mészáros, András Dér, Mára A. Deli, Fruzsina R. Walter
Abstract
The blood-brain barrier (BBB) protects the brain and provides oxygen and nutrients for the central nervous system (CNS), but it also restricts the entry of pharmaceutical drugs into the brain. Cell culture models are essential to investigate cerebral drug delivery. Microfluidic chip devices allow complex and physiological modelling of the BBB. Induced pluripotent stem cell (iPSC) based technologies, the formation and use of human brain organoids provide simplified 3D modeling. Our aim was to (1) create and optimize a new, dynamic cell culture lab-on-a-chip model by the co-culture of a BBB model and human midbrain organoids, and to (2) examine BBB properties and functionality in the presence of organoids. Human stem cell derived endothelial cells and brain pericytes were co-cultured to establish the BBB model (Cecchelli et al., 2014). Human midbrain organoids were differentiated from iPSCs from healthy people and Parkinson's disease patients (Nickels et al., 2020). The barrier integrity of the BBB model was investigated in the presence of midbrain organoids in a dynamic setup by the measurement of impedance and permeability for fluorescent markers. The morphology of brain endothelial cells was examined by immunostaining for tight junction proteins. Functionality of the model was tested by the passage of targeted nanoparticles across the BBB and by characterizing the uptake into the organoids. We found appropriate BBB maturation and integrity in the presence of brain organoids. Nanoparticles crossed and entered the organoids effectively. This complex organ-on-a-chip system can be a valuable tool for further experiments in drug testing.