In vitro human stem cell-based model of non-alcoholic steatohepatitis
Commonly used acronym: NASH model
Scope of the method
- Human health
- Translational - Applied Research
- In vitro - Ex vivo
- Human derived cells / tissues / organs
- Stem cells
- in vitro
- hepatic differentiation
- Drug discovery
- drug screening
- metabolic syndrome
- insulin resistance
Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to severe, life-threatening non-alcoholic steatohepatitis (NASH). Steatosis is mostly asymptomatic and does not cause health complications. However, in 5-10% of the cases it proceeds to NASH in which hepatic inflammation occurs and for which no therapy or drugs currently exist. Today’s investigation of NAFLD and NASH relies mainly on animal models, which are not representative for the human situation. Therefore, we developed a predictive, human-based in vitro model that could be used to investigate molecular mechanisms that drive NASH, identify druggable targets and evaluate potential anti-NASH compounds. The model is based on the exposure (24h) of human skin-derived stem cells (hSKP) differentiated towards hepatic cells (hSKP-HPC) (R. M. Rodrigues et al., Stem Cells Dev. 23, 44–55 (2014)) to factors involved in the metabolic syndrome and hepatic inflammation. The model has proven to be able to detect the anti-NASH properties of a potential anti-NASH drug currently being evaluated in a phase III clinical trial.
- Biosafety cabinet;
- RT-qPCR (+ evt. microarray/RNA-sec facility);
- Fluorescence microscope.
- Still in development
Pros, cons & Future potential
- Resuts within 24 hours;
- Multiple donors can be tested.
The proliferation and hepatic differentiation takes among one month.
The primary application potential of this method is testing potential anti-NASH drugs.
References, associated documents and other information
R. M. Rodrigues et al., Stem Cells Dev. 23, 44–55 (2014)
R. M. Rodrigues et al., Arch. Toxicol. 90, 677–689 (2016). The manuscript for this method has been submitted to Pharmacological Research: Boeckmans, J., Buyl, K., Natale, A., Vandenbempt, V., Rogiers, V., De Kock, J., Marcelino Marcelino Rodrigues, R.* & Vanhaecke, T.* (*Equally contributing senior authors). Elafibranor restricts lipogenic and inflammatory responses in a human skin stem cell-derived model of NASH (Submitted)
Contact personJoost Boeckmans
OrganisationsVrije Universiteit Brussel (VUB)
Pharmaceutical and Pharmacological Sciences
In Vitro Toxicology and Dermato-Cosmetology