Development of complex-shaped liver multicellular spheroids as a human-based model for nanoparticle toxicity assessment in vitro

Toxicology and Applied Pharmacology
Monika Dubiak-SzepietowskaKarl-Heinz Feller

Abstract

The emergence of human-based models is incontestably required for the study of complex physiological pathways and validation of reliable in vitro methods as alternative for in vivo studies in experimental animals for toxicity assessment. With this objective, we have developed and tested three dimensional environments for cells using different types of hydrogels including transglutaminase-cross-linked gelatin, collagen type I, and growth-factor depleted Matrigel. Cells grown in Matrigel exhibited the greatest cell proliferation and spheroid diameter. Moreover, analysis of urea and albumin biosynthesis revealed that the created system allowed the immortalized liver cell line HepG2 to re-establish normal hepatocyte-like properties which were not observed under the conditions of conventional cell cultures. This study presents a scalable technology for production of complex-shaped liver multicellular spheroids as a system which improves the predictive value of cell-based assays for safety and risk assessment. The time- and dose-dependent toxicity of nanoparticles demonstrates a higher cytotoxic effect when HepG2 cells grown as monolayer than embedded in hydrogels. The experimental setup provided evidence that the cell environment ha...Continue Reading

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Citations

Oct 25, 2016·Toxicology·Monika Dubiak-SzepietowskaKarl-Heinz Feller
Jul 8, 2016·Experimental Biology and Medicine·Katrin ZeilingerFanny Knöspel
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