Vall d'Hebron Talks by VHIR 'iPSC- and CRISPR-based 3D brain tissue models recapitulate key features of neurodegenerative and neurovascular diseases'

Speaker: Dr. Dominik Paquet, Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany

Brain research heavily depends on models recapitulating key aspects of human brain physiology and disease pathology. Human iPSCs have great potential to complement existing rodent disease models, as they allow directly studying affected human cell types. In addition, recent developments in CRISPR genome editing revolutionized how impacts of genetic alterations on disease formation can be investigated. Co-culture of disease-relevant iPSC-derived cells with disease-relevant mutations enables studying complex phenotypes involving cellular crosstalk.
By combining iPSC-, CRISPR- and tissue engineering technologies, we established new brain tissue models for AD and FTD using iPSC-derived cortical neurons, astrocytes, and microglia, as well as a microfluidic model of the blood-brain-barrier (BBB) based on co-culture of endothelial cells, mural cells, and astrocytes.
Our technology provides highly controllable and reproducible 3-dimensional tissues with typical cell morphologies and functional features. The brain tissue model displays widespread synapse formation, spontaneous and induced electrical activity, network formation, microglial ramification, tiling, and phagocytosis. It can be long-term cultured in a postmitotic state without proliferation or cell death, thus providing a more controllable, reproducible, and long-lived alternative to cortical organoids currently used for 3D disease modelling. Our fully iPSC-based BBB model forms barrier-containing and perfusable vessels with typical morphologies of all cell types, including formation of astrocytic end feet on the vessels.
Register here to attend by Zoom: https://gencat.zoom.us/j/95402392896