Preclinical animal models of neurological diseases pose limitations primarily because of species differences in developmental mechanisms, tissue architecture, cell types and gene expression. Additionally, it is challenging to model unique human cognitive and behavioral disorders in animal models.1 A viable alternative to study brain development and diseases is the use of brain organoids; miniature brain-like 3D constructs. Human brain organoids have been shown to better mimic brain physiology and function, so they are better models to study neurological diseases and the efficacy of therapies. One challenge of using brain organoids is continued maintenance that requires oxygen and nutrient delivery. Static cultures tend to result in poor gas exchange and waste buildup, leading to cell death in organoids. Organoids grown under perfusion conditions show higher cell viability over a longer period compared to those cultured in static systems.2
It is a two-chamber microfluidics system that incorporates perfusion to simulates the blood flow. The two chambers are separated by a removable and porous membrane that can be seeded with endothelial cells [Figure 3]. Co-culture of endothelial cells with astrocytes and pericytes will enhance the BBB barrier function. This device allows live and post-culture imaging of the 3D culture including staining procedures for tight junction biomarkers, without compromising the cell architecture. It also can be connected to other cell culture systems to mimic multi-organ simulation. Electrodes can be included to measure the transendothelial electrical resistance (TEER) as an endpoint for the barrier function.
- Di Lullo, E., & Kriegstein, A. R. (2017). The use of brain organoids to investigate neural development and disease. Nature reviews. Neuroscience, 18(10), 573–584. https://doi.org/10.1038/nrn.2017.107
- Wang, Y., Wang, Li., Guo, Y., Zhu, Y., et al. (2018). Engineering stem cell-derived 3D brain organoids in a perfusable organ-on-a-chip system. The Royal Society of Chemistry, 8(3), 1677-1685.
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