Related Experiment Video
Updated: Jul 15, 2026
12:40
Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery
Published on: May 19, 2018
Human stem cell-derived hepatic cells recapitulate polygenic risk in MASLD development and highlight CD36 as a key
Alexandra Gatzios1, Marth Stinckens2, Anouk Verhoeven2
1Vrije Universiteit Brussel, Faculty of Medicine & Pharmacy, Department of In Vitro Toxicology and Dermato-cosmetology, Laarbeeklaan 103, 1090, Brussels, Belgium..
Life Sciences
|July 13, 2026
Summary
This study used a genetic risk score in human cells to find new treatments for metabolic dysfunction-associated steatohepatitis (MASH). Silencing CD36 reduced fat buildup and inflammation, identifying it as a promising drug target for MASH.
Area of Science:
- Hepatology
- Genetics
- Pharmacology
Background:
- Metabolic dysfunction-associated steatohepatitis (MASH) impacts patient outcomes, but effective cellular models for target identification are limited.
- Genetic variants influence MASH progression, necessitating research into genetically informed therapeutic strategies.
Purpose of the Study:
- To utilize a polygenic risk score for hepatic fat content (PRS-HFC) in an in vitro human cell model to identify druggable targets for MASH.
- To investigate the role of genetic predisposition in MASH development using a human skin-derived precursor (hSKP) cell-based system.
Main Methods:
- Genotyping of 92 hSKP cell lines and classification based on PRS-HFC.
- Differentiation of hSKP into hepatic progenitor-like cells (hSKP-HPCs) and exposure to MASH-related triggers.
- Assessment of lipid accumulation, inflammation, and transcriptomic alterations, followed by CD36 modulation via siRNA.
Main Results:
- hSKP-HPCs showed a positive correlation between lipid accumulation and PRS-HFC.
- High PRS-HFC correlated with increased interleukin-6 secretion and fatty acid uptake.
- Silencing CD36 reduced lipid accumulation and attenuated MASH-related gene expression, confirming its role in genetic MASH risk.
Conclusions:
- hSKP-HPCs serve as a valid model to study the impact of genetic predisposition on MASH.
- CD36 is identified as a key mediator of genetically driven MASH, presenting a potential therapeutic target.
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