Modelling the Human Blood-Brain Barrier in Huntington Disease.
Domenico VignoneOdalys Gonzalez PazIvan FiniAntonella CellucciGiulio AucielloMaria Rosaria BattistaIsabelle GloaguenSilvia FortuniCristina CariuloVinod KhetarpalCelia DominguezIgnacio Munoz-SanjuanAnnalise Di MarcoPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- blood brain barrier
- endothelial cells
- high glucose
- cerebral ischemia
- stem cells
- oxidative stress
- induced pluripotent stem cells
- end stage renal disease
- vascular endothelial growth factor
- ejection fraction
- chronic kidney disease
- newly diagnosed
- gene expression
- traumatic brain injury
- diabetic rats
- pluripotent stem cells
- single cell
- prognostic factors
- rna seq
- resting state
- peritoneal dialysis
- functional connectivity
- patient reported outcomes
- mesenchymal stem cells
- multiple sclerosis
- drug induced
- cell therapy