Modelling the Human Blood–Brain Barrier in Huntington Disease
Domenico Vignone, Odalys Gonzalez Paz, Ivan Fini, Antonella Cellucci, Giulio Auciello, Maria Rosaria Battista, Isabelle Gloaguen, Silvia Fortuni, Cristina Cariulo, Vinod Khetarpal, Celia Dominguez, Ignacio Muñoz-Sanjuán, Annalise Di Marco
Abstract
While blood-brain barrier (BBB) dysfunction has been described in neurological disorders, including Huntington's disease (HD), it is not known if endothelial cells themselves are functionally compromised when promoting BBB dysfunction. Furthermore, the underlying mechanisms of BBB dysfunction remain elusive given the limitations with mouse models and post mortem tissue to identify primary deficits. We established models of BBB and undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived brain-like microvascular endothelial cells (iBMEC) from HD patients or unaffected controls. We demonstrated that HD-iBMECs have abnormalities in barrier properties, as well as in specific BBB functions such as receptor-mediated transcytosis.