The gut-brain axis (GBA) is a bi-directional communication system that connects the central nervous system and the gastrointestinal tract. This interaction can involve immune, endocrine or metabolic pathways, or the Vagus nerve as the most direct route. The functioning of the GBA is also significantly affected by the bacteria in the intestine, which form the gut microbiome. Dysregulation of the gut-brain axis is implicated in a large number of neurodegenerative diseases and conditions (NDs). For an improved fundamental understanding of the microbiome-gut-brain axis and its functioning in health and disease, we are recreating the GBA using pluripotent stem cells (PSCs). Using PSCs we recreated hippocampal brain organoids, Vagus nerve-like neurons and human intestinal organoids. These organoids will be integrated in a custom microfluidic chip. To model the microbiome, we will introduce intestine-specific bacterial strains to the multi-organ culture on chip.
Microbiome-Gut-Brain Axis on a Chip
The brain is connected to the gastrointestinal tract through bidirectional signaling pathways which are largely regulated by the composition of the microbiota. The goal of this study is to translate the gut-brain axis (GBA) to a microfluidic chip and thus study the complex relationship between the gut microbiome and brain health. We use human pluripotent stem-cell technology combined with relevant on-chip readouts to model the impact of microbiota variation on neuronal functioning in health and disease.
Focused ultrasound treatment on hiPSC derived blood brain barrier model
280.000 patients have Alzheimer’s disease in the Netherlands, however, there is currently no treatment available. Two problems for developing a cure are that therapeutics cannot pass the blood-brain barrier and that current research mainly uses animal models that have different pathophysiological processes.We want to tackle these problems by developing a method for astrocyte differentiation in suspension and applying these cells to a blood-brain barrier model. Using this model, we test and validate focused ultrasound treatment, a technique to temporarily increase barrier permeability using resonating microbubbles. This barrier function is measured by integrating a TEER measuring device.
EFRO – REACT EU
CHD8/7 suppressed BBB-on-chip
It is suggested that mutation in ASD-associated genes CHD8/7 increases BBB permeability. To analyze this phenomenon, a BBB-on-chip with CHD8/7 knockdown needs to be optimized. Co-culture of endothelial cells and astrocytes mimic a simplified barrier function in vitro. CHD8 and CHD7 are silenced with the use of siRNA. Tight junction proteins ensure barrier integrity and their presence during CHD8/7 suppression will be analyzed both in western blot and immunofluorescence.