Engineered Perineural Vascular Plexus for Modeling Developmental Toxicity.
Adv Healthc Mater
; 9(16): e2000825, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32613760
ABSTRACT
There is a vital need to develop in vitro models of the developing human brain to recapitulate the biological effects that toxic compounds have on the brain. To model perineural vascular plexus (PNVP) in vitro, which is a key stage in embryonic development, human embryonic stem cells (hESC)-derived endothelial cells (ECs), neural progenitor cells, and microglia (MG) with primary pericytes (PCs) in synthetic hydrogels in a custom-designed microfluidics device are cocultured. The formation of a vascular plexus that includes networks of ECs (CD31+, VE-cadherin+), MG (IBA1+), and PCs (PDGFRß+), and an overlying neuronal layer that includes differentiated neuronal cells (ßIII Tubulin+, GFAP+) and radial glia (Nestin+, Notch2NL+), are characterized. Increased brain-derived neurotrophic factor secretion and differential metabolite secretion by the vascular plexus and the neuronal cells over time are consistent with PNVP functionality. Multiple concentrations of developmental toxicants (teratogens, microglial disruptor, and vascular network disruptors) significantly reduce the migration of ECs and MG toward the neuronal layer, inhibit formation of the vascular network, and decrease vascular endothelial growth factor A (VEGFA) secretion. By quantifying 3D cell migration, metabolic activity, vascular network disruption, and cytotoxicity, the PNVP model may be a useful tool to make physiologically relevant predictions of developmental toxicity.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Endoteliales
/
Factor A de Crecimiento Endotelial Vascular
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Adv Healthc Mater
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos