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Paper supported long-term 3D liver co-culture model for the assessment of hepatotoxic drugs

Abstract

Preservation of hepatic phenotype and functions in vitro has always been a great challenge for the reconstruction of liver tissue engineering and pharmaceutical researches. Human induced hepatocytes (hiHeps) generated from fibroblasts can be reproducible with nearly normal levels of liver specific functions, which are considered as a new source of hepatocytes for biomedical applications. Moreover, paper has been served as an attractive biocompatible material for cell-based applications. In this study, we established a simple paper-based scaffold array for creating a 3D liver co-culture model that enabled the assessment of drug induced hepatotoxicity. The hiHeps co-cultured with HUVECs exhibited a 3D like morphology and maintained the liver specific functions of producing albumin and urea for up to 2 months. In addition, the hiHeps in this co-cultured model maintained a higher expression of cytochrome P450 genes as compared with monolayer culture on plate and single culture on paper of hiHeps, revealing a marked enhancement of hepatic function in the 3D liver co-culture model. Moreover, the 3D liver co-culture model was exposed to acetaminophen (APAP) and pioglitazone, exhibiting near physiological hepatotoxic responses as compared to the monolayer cultures. Taken together, the low-cost and bioactive paper scaffold could offer great opportunities as 3D in vitro platforms for tissue engineering applications and high-throughput drug testing.

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Publication details

The article was received on 27 Jul 2017, accepted on 24 Sep 2017 and first published on 28 Sep 2017


Article type: Paper
DOI: 10.1039/C7TX00209B
Citation: Toxicol. Res., 2017, Accepted Manuscript
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    Paper supported long-term 3D liver co-culture model for the assessment of hepatotoxic drugs

    J. Qin, Y. Wang, W. su, L. Wang, L. Jiang, Y. Liu and L. Hui, Toxicol. Res., 2017, Accepted Manuscript , DOI: 10.1039/C7TX00209B

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