Using Microfluidic Hepatic Spheroid Cultures to Assess Liver Toxicity of T-2 Mycotoxin

Area of Science:

• Toxicology
• Biotechnology
• Cell Biology

Background:

• Fusarium fungi contaminate cereals and feedstuffs, producing toxic secondary metabolites like T-2 toxin.
• Mycotoxins pose significant health risks, necessitating robust models for toxicological assessment.
• Conventional 3D cell cultures have limitations in mimicking in vivo hepatic complexity.

Purpose of the Study:

• To evaluate the advantages of microfluidic 3D hepatic cultures over conventional methods.
• To establish and assess a 3D co-culture model of hepatic (HepG2) and stellate (LX2) cells for T-2 toxin exposure.
• To characterize T-2 induced changes in metabolizing enzymes and inflammatory markers.

Main Methods:

• Development of microfluidic 3D hepatic co-cultures (HepG2 and LX2 cells).
• Comparison of spheroid formation and functionality in microfluidic versus commercial 3D culture plates.
• Assessment of cell viability, hepatic function, enzyme expression (RT-PCR), and inflammatory markers following T-2 toxin exposure.

Main Results:

• Microfluidic devices facilitated faster and more functional spheroid formation compared to commercial 3D cultures.
• T-2 toxin exposure reduced cell viability and hepatic function in a dose-dependent manner in both monocultures and co-cultures.
• T-2 toxin upregulated Phase I and Phase II hepatic enzyme expression and increased pro- and anti-inflammatory proteins in co-cultures.

Conclusions:

• Microfluidic 3D hepatic cultures provide a superior model for studying T-2 toxin hepatotoxicity.
• The co-culture system effectively recapitulates T-2 induced hepatic dysfunction and inflammatory responses.
• This advanced model aids in understanding the complex mechanisms of mycotoxin-induced liver injury.