Generation of Scalable Hepatic Micro-Tissues as a Platform for Toxicological Studies
10.1007/s13770-020-00272-6
- Author:
Sara DARAKHSHAN
1
;
Ali Bidmeshki POUR
;
Reza KOWSARI-ESFAHAN
;
Massoud VOSOUGH
;
Leila MONTAZERI
;
Mohammad Hossein GHANIAN
;
Hossein BAHARVAND
;
Abbas PIRYAEI
Author Information
1. Department of Biology, Faculty of Science, Razi University, Kermanshah 6714414971, Iran
- Publication Type:ORIGINAL ARTICLE
- From:
Tissue Engineering and Regenerative Medicine
2020;17(4):459-475
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND:Currently, there is an urgent need for scalable and reliable in vitro models to assess the effects oftherapeutic entities on the human liver. Hepatoma cell lines, including Huh-7, show weakly resemblance to humanhepatocytes, limiting their significance in toxicity studies. Co-culture of hepatic cells with non-parenchymal cells, and thepresence of extracellular matrix have been shown to influence the biological behavior of hepatocytes. The aim of this studywas to generate the scalable and functional hepatic micro-tissues (HMTs).
METHODS:The size-controllable HMTs were generated through co-culturing of Huh-7 cells by mesenchymal stem cellsand human umbilical vein endothelial cells in a composite hydrogel of liver-derived extracellular matrix and alginate, usingan air-driven droplet generator.
RESULTS:The generated HMTs were functional throughout a culture period of 28 days, as assessed by monitoringglycogen storage, uptake of low-density lipoprotein and indocyanine green. The HMTs also showed increased secretionlevels of albumin, alpha-1-antitrypsin, and fibrinogen, and production of urea. Evaluating the expression of genes involvedin hepatic-specific and drug metabolism functions indicated a significant improvement in HMTs compared to two-dimensional(2D) culture of Huh-7 cells. Moreover, in drug testing assessments, HMTs showed higher sensitivity tohepatotoxins compared to 2D cultured Huh-7 cells. Furthermore, induction and inhibition potency of cytochrome P450enzymes confirmed that the HMTs can be used for in vitro drug screening.
CONCLUSION:Overall, we developed a simple and scalable method for generation of liver micro-tissues, using Huh-7,with improved hepatic-specific functionality, which may represent a biologically relevant platform for drug studies.
