Adult skin stem cell-derived in vitro model for investigating acute liver failure
Commonly used acronym: hSKP-based ALF model
Scope of the method
- Human health
- Basic Research
- Education and training
- In vitro - Ex vivo
- Human derived cells / tissues / organs
Description
- acute liver failure
- in vitro
- Stem cells
- paracetamol
- in vitro cytotoxicity
- hepatic toxicity
- hepatic in vitro model
- hepatocyte-like cells
This method uses human skin-derived precursors (hSKP) differentiated towards hepatic cells (hSKP-HPC) as a hepatic in vitro model. Exposure of these cells for 24 hours to sub-cytotoxic concentrations of acetaminophen, which is a reference hepatotoxicant, induced specific cellular responses in a comparable way to primary human hepatocytes in culture. APAP-induced gene expression modulation (the read-out of this method) pointed towards an activation “liver damage”, “liver proliferation” and “liver necrosis” and “liver steatosis” were found to be significantly enriched in both in vitro models. This in vitro model, may be used as a surrogate of primary human hepatocytes for the screening of compounds that might potentially induce acute liver failure.
- Biosafety cabinet ;
- Affymetrix microarray platform ;
- Affymetrix Human Genome U133 plus 2.0 arrays ;
- RT-qPCR ;
- Cell culture equipment.
- Published in peer reviewed journal
Pros, cons & Future potential
- Alternative for primary human hepatocytes ;
- Fast method.
Microarray analysis are still expensive and not available in every lab.
QPCR analysis instead of microarrays: selection of specific gene list, that if modulated together would provide the same results.
Other applications, besides drug-induced liver injury should be possible, i.e. for screening of other compounds than drugs.
References, associated documents and other information
Rodrigues et al., Stem Cells Dev. 23, 44–55 (2014)
Contact person
Robim RodriguesOrganisations
Vrije Universiteit Brussel (VUB)Pharmaceutical and Pharmacological Sciences
In Vitro Toxicology and Dermato-Cosmetology
Belgium