In vitro human stem cell-based model of non-alcoholic steatohepatitis

Commonly used acronym: NASH model

Scope of the method

Alternative method relates to
  • Human health
Alternative method is situated in
  • Translational - Applied Research
Type of alternative method
  • In vitro - Ex vivo
This method makes use of
  • Human derived cells / tissues / organs
Specify the type of cells/tissues/organs
Human skin-derived adult stem cells

Description

Method keywords
  • Stem cells
  • Genetics
  • Lipids
  • in vitro
  • hepatic differentiation
  • inflammation
Scientific area keywords
  • NAFLD
  • NASH
  • Drug discovery
  • drug screening
  • preclinical
  • hepatology
  • metabolic syndrome
  • insulin resistance
Method desription

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.

Lab equipment
  • Biosafety cabinet
  • Flow-cytometer
  • RT-qPCR (+ evt. microarray/RNA-sec facility)
  • Fluorescence microscope
Method status
  • Still in development

Pros, cons & Future potential

Advantages
  • Resuts within 24 hours
  • Sensitive
  • Multiple donors can be tested
Challenges

The proliferation and hepatic differentiation takes among one month

Future & Other applications

The primary application potential of this method is testing potential anti-NASH drugs

References, associated documents and other information

References

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)

Associated documents

Contact person

Joost Boeckmans

Organisations

Vrije Universiteit Brussel
Pharmaceutical and Pharmacological Sciences (FARM)
In Vitro Toxicology and Dermato-cosmetology
Belgium