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Toxicology, Dermato-cosmetology and Pharmacognosy (FAFY)

In 2004 a special type of government funding gave birth to the Industrial Research Fund (IOF – Industrieel Onderzoeksfonds). This funding supports the IOF knowledge centers at the Vrije Universiteit Brussel in carrying out outstanding strategic research and further developing new application-oriented inventions with economic potential.

The first priority of the IOF funds is the further establishment of a portfolio of potentially applicable and transferable know-how with economic and societal value.

Keywords

  • progenitor cells
  • adult stem cells
  • histone deacetylase inhibitors
  • DNA methyltransferase inhibitors
  • functional long-term cultures
  • epigenetic modification
  • hepatocyte cultures

Main objectives

The FAFY- team is specialized in the field of in vitro experimental toxicology and is focusing on the development of functional long-term culture models for pharmaco-toxicological purposes applicable at an early stage during the development of new chemical entities as alternatives to experimental animals. In essence, this research offers the key to drastically improve the currently available hepatocyte-based culture systems for in vitro pharmaco-toxicological purposes. The tools developed are not solely based on a descriptive level but offer an explanation at the molecular level as well.

Strategic and applied research

Efforts are being focused on the optimization of primary hepatocyte cultures, as these models are representative for liver, being the pharmaco-toxicological centre of the organism. A well-know drawback of primary hepatocyte cultures, however, is their progressive dedifferentiation (i.e. loss of liver-specific functionality) that FAFY aims to counteract by two strategies :

  1. A first strategy includes the stabilization of primary hepatocyte cultures by the introduction of epigenetic modulation of gene expression. Of special interest is the use of inhibitors of histone deacetylase and DNA methyltransferase enzymes.
  2. A second strategy consists of the differentiation of human adult (postnatal) progenitor cells into functional hepatocytelike cells. Easy accessible cell sources are used including human adipose tissue and foreskin. A unique sequential methodology related to embryogenesis has been developed. This technique of adding growth factors and cytokines can also be combined with epigenetic modification to come to functional cells.

Potentially applicable and transferable know how with economic value

Indeed, FAFY has developed an innovative protocol to produce hepatocyte-like cells out of various sources of adult progenitor cells i.e. sequential exposure of the cells to liver-specific factors according to the sequence seen during embryogenesis. Cells are additionally fully maturated by exposure to epigenetic modifiers such as TSA (patent applications PCT/EP2004/0012134 & PCT/ EP2006/005622).

The robustness of the developed technique is being tested using different sources of progenitor cells derived from different species, including man.

Moreover, the industrial potential of rat-derived RLECs (postnatal stem cells coming from primitive bile cannalicular origin) as a reliable and reproducible source of functional, mature hepatocytes is being investigated. Indeed, the RLECs indicate that their in vitro differentiation into functional hepatocyte-like cells, according to FAFY’s patented sequential culture technique, is reproducible; a feature that is crucial for industrial application. The stem cells are kept undifferentiated while expanded then for a certain number of passages. They can be cryopreserved and/or differentiated according to the needs. Data indicate that the RLEC-derived hepatocytes acquire a normal hepatic morphology, express several liver-enriched transcription factors, secrete albumin and show stable CYP1A1- and CYP2B1/2-dependent activity at a level similar to cultured primary hepatocytes.

Technology Offers

  • Differentiation of stem cells towards hepatocyte-like cells and stabilization of phenotypical properties of primary cells in culture.
  • Differentiation of rat liver epithelial cells into stable hepatocyte-like cells.

Equipment & Infrastructure

Devices that meet the needs of up-to-date experimental research.

Research collaboration

The FAFY team is active in several National and European Associations related to the scientific research topics and knowhow of the group.

Vera Rogiers is, at the European level, co-chair of the SCCS (Scientific Committee on Consumer Safety), member of the mirror group of epaa (The European Partnership for Alternative Approaches to Animal Testing), member of ESAC (ECVAM Scientific Advisory Committee) and coordinator and research partner in several EU projects of FP6 and FP7.

Furthermore, she was leading ecopa, the European Consensus Platform for 3R-Alternative Methods for ten years until start of this year. Regarding the IOF project in particular, close collaboration has been set up at the national and international level.
 

Vrije Universiteit Brussel - Faculty of Medicine and Pharmacy
Laarbeeklaan 103 – B-1090 Jette – Belgium
[W] http://minf.vub.ac.be/~fafy
[T] +32 (0)2 477 45 16
[F] +32 (0)2 477 45 82
Head: Vera ROGIERS
[E] vrogiers@vub.ac.be
GROUP FAFY: 23 people