VUB Technology Offer 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
• 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
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First KIA First KIA Laureate Laureate Fundamental Research Fundamental Research Researcher: Prof. Jhillu Singh Yadav Nationality: Indian Date of birth: 1950 Position: Director Scientiﬁc afﬁliation: Indian Institute of Chemical Technology, Hyderabad, India Project title: Synthesis of complex natural products of biological relevance Abstract