Transgenic Technologies & Tissue Engineering
Modern biotechnological methods present the possibility of direct treatment of illnesses through
gene and cell transfer. The basic objective of this project area lies in the development of
improved procedures of gene and cell transfer. To this end, a tight web of pure research,
industry and clinical application is necessary and envisaged.
TT-Director: Prof. Dr. R. Schüle
Our projects:
Tissue Engineering in reconstructive surgery
Dr. G. Finkenzeller, Prof. Dr. G. B. Stark
The Tissue Engineering Lab was founded in 1994 by Prof. Dr. G.B. Stark. Actually 25 persons including clinicans, natural scientists, technicans, and MD-students are working there in the context of reconstructive surgery. New biological
substitutes will be developed for the restoration, maintenance, modification,
improvement, or replacement of tissues by different methods of tissue
engineering. The idea is to modify existing tissue on the cellular level and to
prepare it for later retransplantation. Overall principle of all research
activities is therefore to take small biopsies from undefected sites, to isolate
tissue specific cells and to expand them to a desired number. The cells are then
either retransplanted directly as a suspension or are combined with an
appropriate matrix to fabricate a three-dimensional construct as shown in the
picture. The construct is implanted directly into the defect or is allowed to grown in vitro before implantation.
Main focus of all research activities are the connective tissues skin, bone, cartilage, muscle, tendon, and fat. Additionallly the group concentrates on the regeneration of peripheral nerves and urothelium. Nearly all projects include studies on angiogenesis. Cell cultures as well as characterization of all tissues mentioned above are established. Additionally
the group has a lot of experience in the field of gene transfer methods. Further activities are biocompatibility testing of new biomaterials and the development and modification of biomaterials as carrier for tissue engineering. Animal models are nude mice, rabbits, rats, and pigs. Collaborations exist to different industry partners as Baxter/Immuno GmbH, BioTissue Technologies GmbH, and Essex Pharma. Until now the group developed one product: Keratinocyte Fibrin Glue Suspension (KFGS) to treat acute and chronic wounds (Stark et al 1992).
Direct contact and further information:
Dr. G. Finkenzeller
Universitätsklinikum Freiburg
Plastische & Handchirurgie
Hugstetterstr. 55
79106 Freiburg
Tel. +49-761-270-6367, Fax. +49-761-270-6368
EMail
Gerichtete Angiogenese im Knochen-Tissue-Engineering
Dr. G. Finkenzeller
Eine der grundlegenden Herausforderungen im Bereich des Tissue Engineering ist die rasche Vaskularisierung der jeweiligen Gewebskonstrukte nach Transplantation, um die Versorgung der transplantierten Zellen mit Sauerstoff und Nährstoffen sicherzustellen und damit ihr Überleben zu gewährleisten.
Ziel des Projektes ist die Induktion von kapillären Netzwerken in gezüchtetem Knochengewebe durch die Kokultivierung und Kotransplantation von Endothelzellsphäroiden in gelartigen Matrixkomponenten. Die gesamten Versuche sind im Hinblick auf eine klinische Anwendung geplant, die durchgeführten Techniken werden nach Möglichkeit im Planungszeitraum schrittweise an GMP-Bedingungen adaptiert werden. In in vitro Versuchen soll die Kokultivierung der verschiedenen Zellpopulationen etabliert und die interzellulären Interaktionen charakterisiert werden. Insbesondere sollen die Konstrukte mittels biochemischen, molekularbiologischen, histologischen und biomechanischen Techniken bezüglich Vaskularisierung, Vitalität, Differenzierung und Stabilität evaluiert werden.
Durch Kombination der in der Gelkomponente immobilisierten Zellen und Kapillarnetzwerke mit einer strukturgebenden Matrix sollen Konstrukte mit für das jeweilige Anwendungsgebiet optimierten Eigenschaften geschaffen werden. Durch Zugabe von angioinduktiven Wachstumsfaktoren (bFGF, VEGF, Angiopoietin-1 und Angiopoietin-2) soll gegebenenfalls die Ausbildung von anastomosierenden kapillären Strukturen weiter gefördert werden.
In in vivo Versuchen soll überprüft werden, ob die Kapillarnetzwerke in den Konstrukten Anschluss an die Zirkulation des Empfängers finden und ob dieser Ansatz zu einer signifikanten Verbesserung der Vaskularisierung der Konstrukte führt.
(English title and abstract following soon)
Direct contact and further information:
Dr. G. Finkenzeller
Universitätsklinikum Freiburg
Plastische & Handchirurgie
Hugstetterstr. 55
79106 Freiburg
Tel. +49-761-270-6367, Fax. +49-761-270-6368
EMail
Identification of genes relevant to organ development and cell differentiation in the functional genomics model organism zebrafish
Prof. Dr. W. Driever
With an ever increasing amount of sequence information for the human genome and that
of various genetic model organisms, the search for identification of gene
function moves into the center of biomedical research. Especially with respect
to organ development, an animal system that is experimentally well accessible
during initiation, morphogenesis and differentiation of organs is desirable.
Zebrafish have evolved over the last two decades into such a model for
vertebrate development, since genetic studies are fast, embryos easily
accessible and transparent, and organ formation highly homologous to mammals.
Moreover, in Germany as well as the US, genome projects have established all the
essential tools, from a high resolution genetic map, EST sequencing project, to
large insert libraries and radiation hybrid panels.
Our laboratory has been involved in developing genetic technology and utilizes
forward genetic approaches to identify genes important for organ development in
vertebrates. Currently we focus on projects in two areas: (1) The identification
of genes involved in specification of the pancreas and differentiation of beta
cells; (2) The identification of genes involved in CNS development, and
specifically of the dopaminergic system. For both projects, genetic screens have
defined a number of mutant loci which appear essential for the proper
development of these systems. Genomic mapping, transcript profiling, the
positional candidate gene approach as well as positional cloning by genomic
walks are employed to identify the genes affected in these mutations. Sequence
conservation has so far consistently enabled us to identify functional
homologues between mammals and zebrafish. The excellent accessibility to
experimental manipulations makes a detailed functional analysis of mutated genes
possible, boss by loss of function genetics as well as gain of function
overexpression studies.
Our projects will advance the understanding of vertebrate organ biology, and help
identify tools to study or treat diseases of the affected organs, like diabetes
or Parkinson disease.
References see .pdf-file
Direct contact and further information:
Prof. Dr. W. Driever
Institut für Biologie I
Hauptstraße 1
79104 Freiburg
Tel. +49-761-203-2587, Fax. +49-761-203-2597
EMail Homepage
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