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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
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
The In Vitro Toxicology and Dermato-
cosmetology (IVTD) group of the Vrije
Universiteit Brussel (VUB) offers an
alternative to primary human hepatocytes.
adult stem cellsin vitro
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
• 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
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
Technology Transfer Interface
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
Fredrik Nicklasson !In November 2013 I started up Scius Pharma Support AB, an independent consulting firm aimed to support product development initiatives of life science companies of all sizes. !Before that, I have worked as line manager, project manager and specialist in the CMC area of the pharma industry for over 13 years. My main expertise lies within the area of formulation developmen
Terashima M, Ikeda K, Maesawa C, Kawamura H, Niitsu Y, Satoh M, Saito K. Establishment of an alpha-fetoprotein-producing gastric cancer cell line in serum-free media. Maesawa C, Mikawa S, Satodate R. Significance of immunohistochemically detected c-erbB-2 protein expression in stage III breast cancer, with reference to nuclear deformity, DNA content and prognosis. Jpn J Clin Oncol 1991;21:264-