3D organoid made of human cells to model the blood-brain barrier and screen drugs
2020
Wake Forest School of Medicine, Winston-Salem, USA
The blood-brain barrier (BBB) comprises a complex arrangement of various cell types which constitute a physical and enzymatic barrier between the brain and the bloodstream. BBB is essential for maintaining the brain's homeostasis. During ischemic stroke, BBB breakdown leads to oedema and haemorrhage which cause major brain damage. The lack of an agreed ischemic stroke model limits the search for molecular therapies. In the present study, the researchers aimed at developing a six cell-type neurovascular unit human organoid model for use in neurotoxicity screening and disease modelling. Human brain microvascular endothelial cells, pericytes, astrocytes, oligodendrocytes, microglia and neurons were obtained from primary material or differentiated from induced pluripotent stem cells. The six cell types were assembled into a 3D organoid in vitro that was then cultured in hypoxia conditions to mimic stroke. The researchers measured changes in expression levels of proteins critical in BBB maintenance/function. The secretion and effect of inflammatory mediators were also assessed. The changes due to hypoxia could be lowered using drugs known to act on hypoxia stress and inflammation, hence validating the model. The study concludes that such neurovascular spheroid is a suitable model for mimicking cerebral pathology, such as hypoxia, that will allow for in vitro testing and the development of novel therapies for diseases of the central nervous system.
Multicellular 3D neurovascular unit model for assessing hypoxia and neuroinflammation induced blood-brain barrier dysfunction
Goodwell Nzou
Added on: 12-20-2021
[1] https://www.nature.com/articles/s41598-020-66487-8
