Using Microfluidic Hepatic Spheroid Cultures to Assess Liver Toxicity of T-2 Mycotoxin
Mercedes Taroncher,
Alan M. Gonzalez-Suarez,
Kihak Gwon,
Samuel Romero,
Angel D. Reyes-Figueroa,
Yelko Rodríguez-Carrasco,
María-José Ruiz,
Gulnaz Stybayeva,
Alexander Revzin,
Jose M. de Hoyos-Vega
Affiliations
Mercedes Taroncher
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55901, USA
Alan M. Gonzalez-Suarez
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55901, USA
Kihak Gwon
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55901, USA
Samuel Romero
Centro de Investigación en Matemáticas Unidad Monterrey, Apodaca 66628, NL, Mexico
Angel D. Reyes-Figueroa
Centro de Investigación en Matemáticas Unidad Monterrey, Apodaca 66628, NL, Mexico
Yelko Rodríguez-Carrasco
Research Group in Alternative Methods for Determining Toxics Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Valencia, Spain
María-José Ruiz
Research Group in Alternative Methods for Determining Toxics Effects and Risk Assessment of Contaminants and Mixtures (RiskTox), Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n, 46100 Valencia, Spain
Gulnaz Stybayeva
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55901, USA
Alexander Revzin
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55901, USA
Jose M. de Hoyos-Vega
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55901, USA
The Fusarium fungi is found in cereals and feedstuffs and may produce mycotoxins, which are secondary metabolites, such as the T-2 toxin (T-2). In this work, we explored the hepatotoxicity of T-2 using microfluidic 3D hepatic cultures. The objectives were: (i) exploring the benefits of microfluidic 3D cultures compared to conventional 3D cultures available commercially (Aggrewell plates), (ii) establishing 3D co-cultures of hepatic cells (HepG2) and stellate cells (LX2) and assessing T-2 exposure in this model, (iii) characterizing the induction of metabolizing enzymes, and (iv) evaluating inflammatory markers upon T-2 exposure in microfluidic hepatic cultures. Our results demonstrated that, in comparison to commercial (large-volume) 3D cultures, spheroids formed faster and were more functional in microfluidic devices. The viability and hepatic function decreased with increasing T-2 concentrations in both monoculture and co-cultures. The RT-PCR analysis revealed that exposure to T-2 upregulates the expression of multiple Phase I and Phase II hepatic enzymes. In addition, several pro- and anti-inflammatory proteins were increased in co-cultures after exposure to T-2.
