Vrije Universiteit Brussel


Research topics

Toxicology

The main research of the FAFY team is situated in the field of in vitro experimental toxicology. Special attention is being paid to the development of liver-based in vitro models for pharmaco-toxicological purposes applicable at an early stage during the development of new chemical entities. Such systems can potentially replace or at least reduce and refine the use of experimental animals. This strategy is in line with the 3Rs principle of Russell and Burch (i.e. replacement, reduction and refinement of animal experimentation). Efforts are in particular 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 is their progressive dedifferentiation (i.e. loss of liver-specific functionality), thereby hampering their long-term use. Yet, three strategies have been introduced to counteract dedifferentiation, based on mimicking the natural in vivo hepatic micro-environment, namely (i) addition of differentiation-promoting soluble molecules to the culture medium, (ii) restoration of cell-cell contacts by co-culturing hepatocytes with another cell type (the so-called “co-culture” system), and (iii) re-establishment of cell-extracellular matrix interactions by cultivating hepatocytes either on one layer of collagen or between two layers as a “sandwich” culture. Over the past years FAFY has extensively studied these in vitro models and has acquired great expertise and international recognition for the development and optimization of long-term primary hepatocyte cultures.

To come to fully functioning hepatocytes in culture, a novel idea was introduced in 1999 and further developed, namely epigenetic modulation of gene expression in primary hepatocyte cultures. Of special interest is the use of inhibitors of histone deacetylase and DNA methyltransferase enzymes, with Trichostatin A and Decitabine as prototypes, respectively, as additives to primary cultured hepatocytes. Several research projects are currently running addressing the impact of epigenetic modifiers on hepatocellular homeostasis i.e. proliferation, differentiation (e.g. biotransformation capacity and gap junctional intercellular communication) and apoptosis. In collaboration with the Department of Organic Chemistry of the VUB, several synthetic analogues of Trichostatin A (TSA), displaying histone deacetylase inhibiting capacity, are investigated.

In 2002, the use of stem cell technology to produce human hepatocytes was introduced.. More specifically, postnatal stem cells from different species and different tissues are differentiated into hepatocyte-like cells by sequential exposure of the cells to liver-specific factors according to liver the sequence seen during embryogenesis. In a second step, the cells are fully maturated by exposure to epigenetic modifiers such as TSA. The thus obtained hepatocyte-like cells have potential for pharmaco-toxicological testing, but also have great value for clinical purposes (i.e. cell transplantation).

The global success of the innovative research carried out by the FAFY team is reflected by a high scientific output and recent patent proposals.

Dermato-Cosmetology

Basic research in the field of dermato-cosmetology

Together with the department of Dermatology of the Universitair Ziekenhuis Brussel, a new research group was established, named SKIN (Skin Research and Physiology), headed by Prof. Diane Roseeuw.
Research projects on the two compartment model of the stratum corneum, unraveling biochemical mechanisms and patho-physiological implications, are running in collaboration with the renowned Department of Dermatology of the University of California (San Francisco, USA). Research is focused on the specific role of skin barrier lipids and on important enzymes in permeability barrier homeostasis and desquamation. Furthermore, the barrier function of the skin – with emphasis on pH, lipid composition and enzymatic systems involved – is studied in order to elucidate mechanisms underlying skin diseases such as atopic dermatitis and the Netherton syndrome.

An improved human skin culture model is developped in which the expertise with the epigenetic modulations, gained during liver research, is applied. This model is used as a research tool to elucidate in vitro the mechanisms of action of dermatologically active molecules in health and disease

Expertise in cosmetic safety assessment and efficacy measurements

With the publication of the 6th amendment to Directive 76/768/EEC, the existence of a complete safety dossier or so-called "Technical Information File" became imperative for cosmetic products brought on the EU market. In answer to this legal requirement, the FAFY research group broadened its existing expertise in safety assessment of cosmetic ingredients (head of department being co-chair of SCCP) towards finished products and the preparation of technical information files (TIFs) according to the European legislation. Consultancy to cosmetic and chemical industry is carried out and yearly a successful one week training course for industry and governmental officials “Safety Assessment of Cosmetics in the EU: Training Course” is organized.
In addition, efficacy measurements of cosmetic products – with up-to-date and validated biophysical techniques – form another important area of expertise of the FAFY group. Non-invasive human in vivo methods, supporting product claims, include skin measurements of transepidermal water loss, hydration, pH, color and micro relief. Also quantification of skin surface lipids and evaluation of stratum corneum desquamation are possible. On top of product testing, these biophysical instruments showed to be appropriate tools to provide functional epidermal barrier parameters in vivo when unveiling various mechanisms involved in the formation and maintenance of the epidermal barrier function. The acquired expertise has proven useful in manifold collaborations with industry and forms an added value to the successful organization of the yearly postgraduate course “Intensive Course in Dermato-Cosmetic Sciences”. The expertise gained over the years is laid down in a handbook "Safety Assessment of Cosmetics in Europe", edited and written by V. Rogiers and M. Pauwels, and brought on the market by Karger, Basel.

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