Engineering human midbrain organoid microphysiological systems to model prenatal PFOS exposure.

Area of Science:

• Neuroscience
• Toxicology
• Biotechnology

Background:

• Perfluorooctane sulfonate (PFOS) is a synthetic chemical linked to human central nervous system (CNS) dysfunction.
• Understanding PFOS neurotoxicology is limited by the lack of appropriate human models.
• Existing models do not fully recapitulate the complexity of fetal human brain responses to environmental pollutants.

Purpose of the Study:

• To develop and utilize bioengineered human midbrain organoid microphysiological systems (hMO-MPSs).
• To investigate the neurotoxic effects of concurrent perfluorooctane sulfonate (PFOS) exposure on a human brain model.
• To establish a scalable and versatile platform for environmental pollutant toxicology studies.

Main Methods:

• Engineered human midbrain organoid microphysiological systems (hMO-MPSs) using 3D printed holder devices for air-liquid interface culturing.
• Scalable and user-friendly hMO-MPS platform compatible with conventional well-plates.
• Integration with a multiple-electrode array (MEA) system for real-time neural activity measurements.

Main Results:

• Exposure to PFOS (0-300 μM) initially increased, then decreased neural activity in hMO-MPSs.
• PFOS exposure was observed to impair neural development in the engineered organoids.
• Neuroinflammation was promoted in the hMO-MPSs following PFOS exposure.

Conclusions:

• hMO-MPSs provide a relevant human model for studying PFOS neurotoxicology.
• PFOS exposure negatively impacts neural development and function, inducing neuroinflammation.
• The developed platform is adaptable for assessing the toxicity of diverse environmental pollutants.