Patterning of interconnected human brain spheroids.

Abstract

Brain spheroids are emerging as valuable <i>in vitro</i> models that are accelerating the pace of research in various diseases. For Alzheimer's disease (AD) research, these models are enhanced using genetically engineered human neural progenitor cells and novel cell culture methods. However, despite these advances, it remains challenging to study the progression of AD <i>in vitro</i> as well as the propagation of pathogenic amyloid-β (Aβ) and tau tangles between diseased and healthy neurons using the brain spheroids model. To address this need, we designed a microfluidic system of connected microwells for arranging two types of brain spheroids in complex patterns and enabling the formation of thick bundles of neurites between the brain spheroids and the accumulation of pathogenic Aβ within the spheroids.