Development of a physiologically relevant test system for the in vitro detection of hepatotoxicity in high throughput (HepatoTox)
HepatoTox is a research network consisting of the BTU Cottbus-Senftenberg (Prof. J.-H. Küpper) and the Fraunhofer Institute for Cell Therapy & Immunology, Division of Bioanalytics and Bioprocesses (IZI-BB) in Potsdam (Prof. C. Duschl). This project is funded by the European Regional Development Fund and the State of Brandenburg.
The main objective is to establish an in vitro high-throughput test procedure for the evaluation of liver toxicity of chemical substances that meets the requirements of the European Union's REACH regulation. The aim of this process is to provide a service to help chemical companies speed up the approval process for newly developed chemicals. The in vitro test procedure should make substantial contributions to the reduction of animal experiments for the evaluation of liver toxicity. The planned project is intended to develop a system to assess liver toxicity of active pharmaceutical substances. This is achieved by new system characteristics, which include:
- Long-term cultivation of human liver cells for more than four weeks, whereby the metabolic activity of the cells is continuously monitored in real time on the basis of their oxygen consumption. This allows the establishment of test formats for the evaluation of chronic or repeated dose liver toxicity.
- Use of human proliferative and physiologically relevant hepatocytes for the evaluation of liver toxicity. These cells have been developed in recent years by Prof. Küpper's research group at the BTU and are characterised by the fact that they represent a much more realistic model system for the liver than other cell lines.
- Adaptation and optimization of the currently available microbioreactor to the requirements of proliferative physiologically relevant human liver cells. So far, the reactor and its supply infrastructure have been used for a common liver cell line that is much easier to cultivate.
- Extension of the fluidic and optical infrastructure for the parallel operation of 12 microreactors.
Duration: 2017-2021
PERsonalized Medicine by FUNCTIONomics in BB: Drug-Metabolism Module for Drug Testing on Patient Cells
PER-FUNCTION BB is a research network consisting of the BTU Cottbus-Senftenberg (Prof. K. Scheibner and Prof. J.-H. Küpper) and the University of Potsdam (Prof. F. Jung and PD. Dr. Burkard Schulz). This project is funded by the European Regional Development Fund and the State of Brandenburg.
The innovative research approach will increase the possibilities of companion diagnostics, i.e. stratification of patients with regard to their response to a therapy, which is currently mainly carried out at the genome and protein level. The new technology platform will add to genomics, metabolomics and proteomics by patient-individualized in vitro drug tests and is called "FUNCTIONOMICS". The essential prerequisite for FUNCTIONOMICS, which can be realized in the submitted research concept, is that not only the respective active substance is investigated on patient cells, but also drug metabolites produced in the liver can be tested preparatively for the first time.
Duration: 2016-2020
Collaborative project to establish a Brandenburg Health Campus "Consequences of age-associated cell and organ functions
The joint project "Consequences of age-associated cell and organ functions" (http://www.mwfk.brandenburg.de/cms/detail.php/bb1.c.432526.de) deals with scientific and clinical challenges in three thematic areas. The network for subproject 1.1 Age-dependent liver and endothelial functions consists of the BTU Cottbus-Senftenberg (Prof. J.-H. Küpper), the Helmholtz Zentrum Geesthacht (HZG) in Teltow (Prof. F. Jung), the Fraunhofer Institute for Cell Therapy and Immunology (IZI-BB) in Potsdam (Dr. C. Duschl) and the University of Potsdam (Prof. G. M. Püschel).
The project addresses the general medical problem of adverse drug reactions (UAWs). Due to the direct metabolization of most drugs in the liver, UAWs occur there most frequently. However, the drugs or their liver metabolites can damage other organs after transport via the circulatory system and, of course, directly the blood vessels. Individual drug effects therefore depend heavily on liver function, which can be dramatically impaired by genetic predisposition, age, previous illnesses and multimedication. A concept for predicting individual drug effects on liver and endothelial function on the basis of relevant in vitro systems with primary cells will be developed. In addition, the age dependence of liver functions in the animal model will be investigated.
Duration: 2016 - 2018