PD Dr. Andrea Banfi, Group Leader, Cell and Gene Therapy, University Hospital Basel/CH _
Vascularization in Regenerative Medicine
The need to rapidly vascularize tissue-engineered grafts is one of the major limiting factors towards their clinical implementation. Therapeutic angiogenesis aims at restoring blood flow to ischemic tissues by the generation of new vessels. Our research focuses on understanding the basic principles governing the growth of blood vessels and translating this knowledge into rational therapeutic approaches to both treat ischemic diseases and improve the vascularization of tissue-engineered grafts.
To this end, precursor cells are genetically engineered to express controlled levels or combinations of angiogenic factors, in order to provide both vascular growth and tissue regeneration, combining the specific advantages of cell and gene therapy. Here I will present some approaches we have recently developed to control vascularization for the regeneration of bone, heart and cartilage, based on the combination of progenitors with either gene delivery vectors or smart biomaterials.
Prof. Christian De Geyter, Chefarzt Gynäkologie, Endokrinologie und Reproduktionsmedizin, Forschungsleiter Dept. Forschung, University Hospital Basel/CH
Use of stem cells in developmental toxicology
Our commitment in stem cell technology began shortly after the installment of a new legislation allowing the derivation human embryonic stem cell (hESC) lines from embryos in 2003 in Switzerland. Together with colleagues at the University Hospital of Geneva we initiated a comprehensive program to develop the derivation, the maintenance and the characterization of genuine Swiss hESC lines from supernumerary embryos arising during assisted reproductive technology (ART). Our endeavor resulted in the production and characterization of five Swiss hESC lines with normal chromosome complement, which are now being used in various research projects in Geneva, Lausanne and Basel. Not only did our experience with this technology improve the quality and outcome of clinical ART, but also lead to the establishment of qualified protocols for the derivation of induced pluripotent cell lines (iPS) from human somatic cells.
In a second step we embarked on developing protocols for the use of hESC lines as an in vitro model of early embryonic growth aiming at setting up novel methods for reproductive toxicology testing. Currently early developmental toxicity testing of existing or novel chemical and/or pharmaceutical products is being carried out in animal models, most commonly rats. Apart from being extremely costly and animal consuming, the results of such testing may not always be applicable to the human.
Controlled in vitro differentiation of hESC mimics many aspects of early embryonic growth and may potentially be used for developmental toxicity testing in vitro. However, many aspects of this principle are still unknown, most notably known differences in the properties of existing cell lines and individual propensity for (pre)differentiation.
In order to study the feasibility of developmental toxicity testing using existing hESC lines we used default neural differentiation of stem cells as a model for neural tube closure defects (e.g. spina bifida), known to be caused by drugs such as valproic acid (VPA) and cyclopamine (CPA). The effects of those toxicants (and control chemical substances) on a number of aspects of neuroectodermal cells towards neural cells were assessed using our four different hESC lines, all developed under identical conditions in our laboratory. Despite those preconditions, we observed significant differences in the sensitivity of each of those lines to the toxic effects of VPA and CPA. The mechanisms responsible for these observed differences are currently being examined. Pre-differentiation being more pronounced in some lines but not in others is one chief mechanism.
With the proof of feasibility resulting from neurotoxicology testing we will soon embark on setting up protocols for reproductive toxicology, using testicular dysgenesis as our starting hypothesis. We will develop protocols to differentiate hESC to primordial germ cells (PGC) checking differences in epigenetic signatures in the presence of endocrine disruptors as the main readout. All toxicology studies are being carried out under the supervision of the Swiss Center of Applied Human Toxicology (SCAHT)
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