Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure.
Sci Total Environ
; 947: 174478, 2024 Oct 15.
Article
de En
| MEDLINE
| ID: mdl-38964381
ABSTRACT
Perfluorooctane sulfonate (PFOS), a class of synthetic chemicals detected in various environmental compartments, has been associated with dysfunctions of the human central nervous system (CNS). However, the underlying neurotoxicology of PFOS exposure is largely understudied due to the lack of relevant human models. Here, we report bioengineered human midbrain organoid microphysiological systems (hMO-MPSs) to recapitulate the response of a fetal human brain to multiple concurrent PFOS exposure conditions. Each hMO-MPS consists of an hMO on a fully 3D printed holder device with a perfusable organoid adhesion layer for enhancing air-liquid interface culturing. Leveraging the unique, simply-fabricated holder devices, hMO-MPSs are scalable, easy to use, and compatible with conventional well-plates, and allow easy transfer onto a multiple-electrode array (MEA) system for plug-and-play measurement of neural activity. Interestingly, the neural activity of hMO-MPSs initially increased and subsequently decreased by exposure to a concentration range of 0, 30, 100, to 300 µM of PFOS. Furthermore, PFOS exposure impaired neural development and promoted neuroinflammation in the engineered hMO-MPSs. Along with PFOS, our platform is broadly applicable for studies toxicology of various other environmental pollutants.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Mésencéphale
/
Organoïdes
/
Acides alcanesulfoniques
/
Fluorocarbones
Limites:
Female
/
Humans
/
Pregnancy
Langue:
En
Journal:
Sci Total Environ
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique