A DMSO-free hepatocyte maturation medium accelerates hepatic differentiation of HepaRG cells in vitro
| Autor: | Wei-Jian Li, Gong-Bo Fu, Hong-Shu Jing, Qi-Gen Li, Tian-Jie Yuan, Hong-Dan Zhang, Zhen-Yu Wang, Bo Zhai, He-Xin Yan, Dan Tang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
3D culture Hepatocyte maturation medium Cellular differentiation RM1-950 Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine DMSO-free In vivo medicine Humans Dimethyl Sulfoxide Progenitor cell Pharmacology Chemistry Dimethyl sulfoxide Hepatotoxicity Cell Differentiation General Medicine In vitro Cell biology Culture Media 030104 developmental biology medicine.anatomical_structure Liver 030220 oncology & carcinogenesis Hepatocyte Toxicity Hepatocytes Therapeutics. Pharmacology HepaRG Drug metabolism Glycogen |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 116, Iss, Pp 109010-(2019) |
| ISSN: | 1950-6007 |
| Popis: | The most essential tools for studying drug hepatotoxicity, liver diseases, and bioartificial livers have always been models that can recapitulate liver physiology in vitro. The liver progenitor cell line HepaRG represents an effective surrogate of the primary hepatocyte. However, the differentiation of HepaRG relies on long-term induction using a high concentration of dimethyl sulfoxide (DMSO), which may compromise the research of drug metabolism and restrict the applicability of this hepatic model. Here, we present a novel hepatic maturation medium (HMM) for the differentiation of HepaRG, which is based on a cocktail of soluble molecules that mimick the in vivo environment. We showed that HMM could rapidly (about nine days) induce HepaRG differentiation into polarized hepatocytes with maturely metabolic functions. In addition, under three-dimensional culture conditions, the hepatic spheroids showed multiple liver functions and toxicity profiles close to those of primary human hepatocytes (PHH). Our work demonstrates the utility of HMM as an alternative to the DMSO-dependent differentiation protocol for HepaRG; moreover, these results facilitate the application of HepaRG. |
| Databáze: | OpenAIRE |
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