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Demand for human-
relevant hepatic in
vitro models for safety
Human-relevant hepatic system
testing of drugs
derived from adult stem cells
A protocol was established based on the state of the art knowledge of liver development and epigenetic mechanisms of gene regulation. Accordingly, to obtain human hepatocyte- like cells, postnatal stem cells are exposed to specific growth factors and cytokines
in a sequential and strictly time-bound manner. By addition of epigenetic modifiers
Indeed, the hepatotoxic potential of new the acquisition of a hepatocyte-like gene expression pattern is facilitated.
drug candidates is difficult to predict using animal models, as carried out today, Using this protocol, hepatocyte-like cells are obtained that adopt cuboidal cell morphology, typical for mature hepatocytes, and express among others: hepatic in vitro systems could overcome • the key hepatic cytoskeleton protein and major plasma proteins (Fig 1).
this limitation. The use of isolated human hepatocytes remains the most common Moreover, these hepatocyte-like cells demonstrate the functionality of: approach, yet it is largely limited by an • drug transporters and drug metabolizing enzymes erratic availability of liver donors, as well • urea and albumin secretion ability.
as progressive dedifferentiation and short lifespan of primary cells in in vitro setting. Yet the most important, hepatocyte-like cells generated by this methodology respond
Consequently, human stem cells, induced
in a similar way to prototypical liver toxicants, e.g. acetaminophen, as primary human
to differentiate towards hepatic phenotype,
hepatocytes in culture.
have become an attractive cell source
to develop human-relevant liver in vitro
models for the safety assessment of new
drug candidates.
The In Vitro Toxicology and Dermato-
cosmetology (IVTD) group of the Vrije
Universiteit Brussel (VUB) offers an
alternative to primary human hepatocytes.
Keywords
adult stem cells
in vitro liver models
hepatocyte-like cells
hepatic differentiation
Figure 1:
Expression of albumin by hepatocyte-like cells derived respectively from (i) bone marrow (rMPC:
rat mesenchymal progenitor cells and hMSC: human mesenchymal stem cells ), (ii) cells of biliary origin (rLEC: rat liver epithelial cells) and (iii) skin (hSKP: human skin-derived precursors).
VUB Technology Offer
Innovation with competitive advantages
IP status
• not hindered by species-specific barriers and thus applicable to human and animal
- Granted EP patent "Differentiation of stem postnatal stem/progenitor cell cultures (Fig. 1) • use of easily accessible and ethically uncontroversial stem cell sources
properties of primary cells, EP1824965 (B1) • initial stem cell populations can be expanded according to the needs
• successful hepatic differentiation of postnatal stem/progenitor cells derived from
various tissues, including bone marrow, adipose tissue, skin and bile duct
• no genetic manipulation required
• proved applicability of obtained hepatocyte-like cells in a 'real life' toxicological
Interested parties
can contact
Technology Transfer Interface
Market opportunities
Product development asks for functional and stable in vitro models for safety and/or efficacy testing. Therefore, hepatocyte-like cells derived by means of above described hepatic differentiation technology could have high impact on: • the cosmetic industry, where animal testing and marketing bans became final in
In Vitro Toxicology and
March 2013, irrespective of the availability of alternative non-animal tests Dermato-cosmetology (IVTD)
• the pharmaceutical industry, where in vitro methods become key for early
decision making in the drug development process due to their speed, high • the chemical industry, where safety testing under REACH is associated with
substantial financial costs and high animal consumption.
Dr. Joanna Fraczek Business Development Manager What are we looking for?
[T]: +32 (0)2 47745 20[E]: Joanna.Fraczek@vub.ac.be • Out-licensing of the hepatogenic differentiation technology (EP1824965 (B1)) • Setting up joint R&D projects with industrial partners to develop toxicological assays based on hepatocyte-like cells obtained with our hepatogenic differentiation • Providing of expertise in the area of (hepatic) stem cell differentiation technologies on the fee-for-service or collaborative basis.
Customer-tailored solutions are also discussable.
Technology Transfer Interface • R&D DepartmentVrije Universiteit Brussel • Pleinlaan 2 • B-1050 Brussels • Belgium[W] www.vubtechtransfer.be • [T] +32 (0)2 629 22 07

Source: http://vubtechtransfer.be/medialibrary/TOP_IVTD_From%20adult%20stem%20cells%20to%20hepatocytes.pdf