Venue of this year’s World Congress on Alternatives and Animal Use in the Life Sciences: Prague; view across the Vltava with the famous Charles Bridge and the historic Castle District.
Photo: Christiane Hohensee


A notable focus this year was the current stage of development of human cell culture models in miniature format (multiple organ-on-a-chip systems). The goal is to be able to present about 10 different artificial “organs” on a microchip by the end of 2017. In addition to Germany, especially the USA, Russia, the Netherlands, Japan and Switzerland are working on this subject.

The company TissUse in Brandenburg, for example, has in collaboration with the TU Berlin now succeeded  in connecting two organs (liver and skin, liver and nervous cell system) via a miniature vessel system and reliably using them for testing for chemicals or pharmaceutical substances. A combination of 4 different cell systems has successfully been implemented.  The cultures can also be cultivated for longer periods (i.e. 28 days) and used for repeated dose experiments.

Human-on-a-Chip: A TissUse employee holding a platform.
Photo: Christiane Hohensee


At the National Institute of Health, these human “organs” currently comprise either progenitor cells, differentiated cells or a combination of both. The cells are applied to a framework in order to give them a three-dimensional shape. The goal is to achieve the human “body-on-a-chip” within 5 years. The roadmaps presented in the papers gave the impression that increasing technological progress has accelerated the development of these systems: Validation of the first systems is planned for as early as 2018. They are to be used for testing chemicals and in the pharmaceutical industry. Nonetheless, some scientists are cautious with regard to the suitability of their microchip systems and consider the production of “mouse-on-a-chip” and “rat-on-a-chip” systems – i.e. the use of tissue from mice and rats – to be necessary in order to be able to compare the results with those obtained in animal experiments.

Despite initial miniature setups with human disease-on-a-chip models (cell tissue models for investigating the fundamental mechanisms of human diseases), the implementation of the chip models is currently intended less for use in basic research than in toxicological tests for cosmetics, the evaluation of chemicals or the development of pharmaceutical drugs. Conversely, this means that a continued development of animal models must be expected.

In a talk on refinement,  S.-W. Lin from the National Taiwan University in Taipei reported that the numbers of animals used could be reduced by 85 per cent using a new method for producing genetically modified mice. The method is called CRISPR/CAS9 and has the goal of helping to reduce the risk of undesired mutations in the production of mouse models. CRISPR is a modern gene editing method comprising a ribonucleic-guided platform that uses a bacterial protein known as Cas9 and a synthetic guide-RNA to cause a double-strand break at a specified DNA site. The cell is transfected at the desired site creating a new pair bond at the strand break. Critical scientists consider a reduction in the claimed magnitude to be improbable, as the insertion  (knock-in) of an additional gene sequence can cause multiple mutations.

A number of scientists presented research results in the field of developmental neurotoxicity, for instance Elaine Faustman from the University of Washington in Seattle. In order to assess the relevance of human neural progenitor cells (hNPCs), her team differentiated the hNPCs for up to 21 days and evaluated changes in protein expression by western blotting and immunofluorescence. It was found that 90 per cent of the genes were expressed both in vitro and in vivo. Andrea Seiler from the German Federal Institute for Risk Assessment in Berlin presented results from developmental neurotoxicity tests using murine embryonic stem cells, which had been compared with the results of animal tests (in vivo). The test’s results for the investigated substances closely matched  the in vivo results. The research group next wants to use embryonic stem cells to develop a more complex tissue for simulating a CNS-like situation, which could then be used for investigating developmental neurotoxicity.

Not only the brain and nerves were a topic at the congress. A research group from the University of Nottingham presented a 3D cell culture using fibroblasts from the human lung to simulate the lung’s reaction to inflammatory processes.

A remarkable paper was presented by Philip Morris International Research & Development in Switzerland. To assess the effect of cigarette smoke on the upper respiratory tract via oxidative cellular stress and inflammatory processes, the scientists developed a test system based on human nasal epithelial tissue. The mixture of various toxic substances also contains hydrogen cyanide which, depending on time and dose, led to the release of inflammation markers, the activation of xenobiotic metabolising enzymes and altered gene expression.

Troy Seidle from the Humane Society International provides insights into how complex and comprehensive cellular metabolic pathways are.
Photo: Christiane Hohensee


Another strongly represented topic was the ethical evaluation of animal experiments. Article 38, paragraph 2, subparagraph d of the European Directive on the protection of animals used for scientific purposes requires a harm-benefit analysis for projects. So far, European scientists and government agencies have not reached an agreement on what such an evaluation should look like. Various researchers are considering how to weight up the harm of animals in animal tests submitted for approval and the claimed benefit as well as the probability of success.

Norbert Alzmann outlines the current Austrian Catalogue of Criteria to objectify the harm-benefit analysis of proposed animal experiments.
Foto: Christiane Hohensee


Several research teams have developed varyingly intensive approaches for harm-benefit analyses, whereby the system currently being developed by Norbert Alzmann, Vera Marashi and Herwig Grimm and due to be published at the end of 2015 is the most comprehensive.

All the abstracts have been published by ALTEX in a proceedings book. You can download and read it here:
http://www.altex.ch/ALTEX-Proceedings/Proceedings.98.html?iid=4