Human stem cell-based platform for the early detection of drug-induced liver injury (DILI)

Drug-induced liver injury (DILI) represents a major problem worldwide for both the pharmaceutical industry and regulatory authorities. Hepatotoxicity is the leading cause of drug withdrawal from the market. Consequently there is an urgent need for improved sensitivity in the identification of hepatotoxic compounds, in human cells, at a much earlier stage in the drug development process.

Solution: adult human skin-derived stem cells differentiated towards hepatic cells

Adult human skin-derived stem cells differentiated towards hepatic cells (hSKP-HPCs, pictured above) are ethically sound, conveniently accessible and highly sensitive hepatic cells. Using the proprietary differentiation technology of the In Vitro Toxicology and Dermato-cosmetology (IVTD) research group of the VUB, they can be easily produced from human donors in health and disease. Their derivation method and unique sensitive profile, positions them as a valuable new tool for human focused DILI investigations.

A Unique Hepatic Model:

  • Early stage phenotype, between embryonic and adult hepatic cells, confers a commitment to hepatic development in culture, enabling the accurate detection of toxicity earlier than in current industry models.
  • The onset of steatosis can be detected very early at the transcriptional level, even before the accumulation of lipid droplets, a hall mark of human steatosis, in response to sodium valproate (see figure).
  • Responsive to other liver toxicants, including acetaminophen (acute liver failure inducer) and amiodarone (steatosis and phospholipidosis inducer).

Competitive advantages over other hepatic models

  • easily accessible and highly expendable, human cell source which maintains hepatic phenotype during long-term culture ( > primary hepatocyte cultures)
  • hepatic cultures can be derived from any human donor in health and disease, ( > hepatic cell lines)
  • ethically sound derivation (> embryonic stem cells derived hepatic models)
  • no genetic manipulation required ( > iPSCs-derived hepatic models)

Valuable for the early detection of DILI towards safety testing in:

  • the cosmetic industry
  • the pharmaceutical industry
  • the chemical industry

Interested parties can contact

VUB TechTransfer
Hugo Loosvelt
[T]: +32 (0)2 629 38 65 or 22 07
[E]: hugo.loosvelt@vub.ac.be

In Vitro Toxicology and Dermato-cosmetology (IVTD)
Vera Rogiers
[T]: +32 (0)2 47745 16
[E]: vera.rogiers@vub.ac.be
Ruani Fernando
[T]: +32 (0)2 47745 20
[E]: ruani.fernando@vub.ac.be

Patent details

Granted patent application EP1824965 (B1), titled “Differentiation of stem cells and stabilization of phenotypical properties of primary cells”, validated and maintained in UK, Germany and France.

Download a printable pdf here.