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New Scientific Adviser and Chairman of the Evaluation Committee (February 2013)
The Administrative Board has appointed Prof. Ernst B. Hunziker, head of the Center of Regenerative Medicine for Skeletal Tissues at the University of Berne, to take over as Scientific Adviser and Chairman of the Evaluation Committee on 1 March 2013.
Evaluation Committee

Resignation of Prof. Peter Maier as Scientific Adviser and Chairman of the Evaluation Committee (December 2012)
Prof. Peter Maier retired at the end of 2012, having been involved with the 3R Research Foundation for 12 years. During that time he helped the Foundation develop into an institution that is recognised by academic researchers throughout Europe. The Administrative Board would like to extend their sincerest thanks to Prof. Maier for his fruitful work and wish him every success with his future career as a toxicologist at the University of Zurich.

3R - Still relevant twenty-five years on; 25 years of Funding the 3Rs (December 2012)
3R-Info-Bulletin 50
Prof. Peter Maier, Scientific Adviser of the 3R Research Foundation in Switzerland, reflects on the visibility, activity and future role of the Foundation.
Dr. Stefanie Schindler, an animal welfare expert, assesses the Foundation’s twenty-five years of funding.
To mark the Foundation’s 25th anniversary, the two authors describe the present situation with regard to animal experimentation in Switzerland (awareness of the Foundation’s work, limited funds) and the progress achieved so far concerning reduction und refinement.
In order to prevent an increase in the use of laboratory animals in the field of life sciences, the established research promotion involving live animals should specifically support aspects relevant to the 3R principles. A study is under way to analyse what the 3R Research Foundation has achieved over the past 25 years in various fields through its albeit limited funding; initial results are published.
3R-Info Bulletin 50

Completion of a project (December 2012)
Use of "moribund" stage in the acute fish toxicity test according to OECD guideline 203 and its effect on LC50 values
Dr. Hans Rufli, ecotoxsolutions, Basle, Switzerland
The aim of this project is to define the final ”moribund” stage in the acute toxicity test in fish in order to introduce it as a criterion for interrupting the test under OECD guideline 203. Retrospective analysis of data and protocols from hundreds of toxicity tests carried out on fish has shown that by introducing the “moribund” criterion the suffering of the fish through the acute effects of a test substance could be reduced by up to 92 hours thanks to its earlier removal from the test. By introducing the “moribund” criterion, the LC50 value could be lowered, on average by a factor of 2, in up to half of the experiments. Attempts are now being made, in collaboration with the Swiss Federal Office for the Environment and various EU countries, to get the OECD protocol changed. This would help to achieve a significant reduction in the level of suffering among the fish used in this test.
Project 123-10

Completion of a project (December 2012)
A new in vitro model to study therapeutic approaches to improve spinal cord regeneration and repair after injury
Prof. Roman Chrast, Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
This project aimed to examine the effect of various substances on spinal cord regeneration in vitro using mouse organotypic longitudinal, sagital slice cultures developed by the project leaders. The research team was also able to induce lesions similar to those seen in multiple sclerosis, thus allowing for functional and structural studies. Using this method it would be possible to avoid a large number of tests on live animals. Comparative in vivo and in vitro studies using potential new medicines remain to be carried out.
Project 121-10

Completion of a project (December 2012)
Development of non-invasive strategies to study spinal cord disease, injury and repair
Prof. Denis Jabaudon, Neuroscience Department, University Medical Centre, University of Geneva, Geneva, Switzerland
In this project, Prof. Jabaudon aimed to develop a method for the non-invasive injection of substances (e.g. plasmids) into the spinal cord of mice without using a surgical procedure. Such a method would result in a lower rate of mortality and less suffering among the laboratory animals used. The research team was able to demonstrate that the high-resolution ultrasound method for positioning the hypodermic needle for cortical injections was equally as accurate as the stereotactic method. On the other hand, the ultrasound method proved to be unsuitable for spinal injections. It was therefore not possible to establish the non-invasive injection method for use in the spinal cord.
Project 120-10

Completion of a project (December 2012)
Engineering of an in vitro hepatocyte tissue system for malaria liver infection research
Dr. Dalu Mancama, Biosciences Division, Systems Biology, CSIR, Pretoria, South Africa
With this project, the researchers aimed to develop a hepatocyte tissue culture system using human liver cells for the purpose of studying the primary infection process of malaria (infection with plasmodium sporozoites isolated from the Anopheles mosquito) and the proliferation of the parasites in cultured liver cells. The ultimate aim would be to develop vaccines, prophylactic medicines and an acute chemotherapy without using laboratory animals. The main stages of the study were successfully completed. The in vitro culture (proliferation) of the asexual stage of Plasmodium falciparum with erythrocytes, the culture of human hepatocytes with sporozoites and the co-culture with infected erythrocytes were all successful. The rate of infection observed was low and was influenced by the culture conditions. Further verification of the results will be carried out.
Project 118-10

Completion of a project (December 2012)
Engineering of a human brain tumor model to replace animal experimentation
Prof. Olivier Preynat-Seauve, Department of Pathology and Immunology, University Medical Centre, University of Geneva, Geneva, Switzerland
The aim of this project was to combine the delicate cell culture models developed by the project leader for brain tissue (engineered neural tissue, ENT, from embryonic stem cells) and glioblastomas (engineered glial tumors, EGT, from human tumor tissue), and thus to develop an in vitro system for studying glioblastomas and characterising their molecular structure. Such a system would replace in vivo methods that cause considerable suffering to the laboratory animals used, in particular in relation to the intracerebral or subcutaneous injection of human tumor cells in immuno-suppressed mice. The team were successful in establishing their in vitro system. Histo-pathological and molecular-biological studies were carried out on the reaction of the EGT transplanted into the ENT. It now remains to examine the various ways in which this model can be used.
Project 115-09

Completion of a project (December 2012)
Generic in vitro evaluation assay for immunological correlates of protection, to replace animal challenge infection
Dr. Artur Summerfield and Dr. Kenneth McCullough, Institute of Virology and Immuno-prophylaxis (IVI), Mittelhäusern, Switzerland
The aim of this project was to provide a reliable and fast in vitro test to replace in vivo testing by which live animals suffer considerably through being exposed to vaccines in order to match a potential vaccine to the current serotype of foot-and-mouth disease virus in the field. The researchers were able to measure a response specific to the virus type in cultures of specialised immune cells. By using genetically modified cells it was possible to further simplify and improve the test. This provides a scientific basis for developing reliable tests based on cell lines. The new test will now be further validated by a European consortium (FMD-DISCONVAC).
Project 113-08

25th Anniversary of the 3R Research Foundation (November 2012)
In the interests of the welfare of laboratory animals
For the past 25 years the foundation has been funding research into better or alternative methods to animal experimentation. To mark this anniversary it was organising a training course in the Technopark in Zurich, together with the Swiss Laboratory Animal Science Association. The media information published on 20.11.2012 provides the general public with an insight into the Foundation’s long commitment to animal protection and science.

Media release (PDF)
Background information for the Jubilee (PDF)

Six examples of research projects funded by the Foundation:
Observing rats using magnetic resonance imaging (MRI) (PDF) – Refine, Reduce (Project 82-02)

Behavioural studies to reveal mild pain in mice (PDF) – Refine (Project 71-00)

Cell culture systems for estimating the risk of inhaled (nano-) particles to replace inhalation experiments involving laboratory animals (PDF) – Reduce, Replace (Project 89-03)

It is possible to test the suitability of stem cells for treating brain damage using brain slices in cell culture (PDF) – Reduce, Replace (Project 103-06)

By using cells instead of pigs, it is possible to estimate the virulence of the classical swine fever virus (PDF) – Reduce (Project 105-06)

Testing for acute toxicity in fish: Fewer fish and less suffering (PDF) – Reduce, Refine (Project 114-08, Project 123-10)



New project (August 2012)
Development of a cardiovascular simulator with autoregulation
Prof. Dr. Stijn Vandenberghe, ARTORG Center for Biomedical Research, University of Berne, Switzerland
Many studies are carried out in vivo for testing and gaining regulatory approval for cardiological devices. The aim of this project is to adapt a cardiovascular simulator to in vivo conditions in such a way that far fewer laboratory animals are required for testing such devices as blood-pumps, for example. The challenge in this case is to simulate self-regulating, clinically relevant mechanisms such as baroreflex (blood pressure and heart beat regulation) and the Frank-Starling mechanism (correlation between inflow and expulsion). The (preliminary) testing of devices using such further developed simulators should help to ensure that only the most promising devices are tested in vivo.
Project 134-12

New project (August 2012)
Development of an vitro system to grow and investigate vascular endothelial cells under physiological flow
Prof. Dr. Robert Rieben, Department of Clinical Research, University of Berne, Switzerland
The function of endothelial cells in the walls of blood vessels is often investigated in vivo, causing suffering to the laboratory animals involved. Conventional in vitro procedures simulate the physiological conditions with inadequate accuracy. This new in vitro experimental method is aimed at replacing many such in vivo studies. In the proposed in vitro model the pressure and shearing power of the pulsating blood, for example, are simulated. This system should make it possible to find answers to questions concerning ischaemia, reperfusion and transplantation that have so far been investigated in in vivo experiments involving considerable pain and suffering for the laboratory animals concerned.
Project 133-12

New project (August 2012)
Identification of predictive in vitro markers for hematopoietic stem cell function
Prof. Dr. Matthias P. Lutolf, Institute of Bioengineering, EPFL, Swiss Federal Institute of Technology Lausanne, Switzerland
In order to test whether hematopoietic stem cells (HSC) are capable of producing normal blood cells over a longer period of time, they are normally implanted into mice. Measurements are then made to see whether the HSC are able to reconstitute the blood system that has been destroyed through radiation. This procedure causes extreme suffering to the animals used and a large number of mice have to be sacrificed. In this project, Prof. Lutolf and his team intend to identify new cell markers to predict the long-term functioning of HSC that have been developed in vitro.
Project 132-12

New project (August 2012)
Antibody phage selection strategy for application in non-specialized laboratories
Prof. Dr. Christian Heinis, Laboratory of Therapeutic Peptides and Proteins, EPFL, Swiss Federal Institute of Technology Lausanne, Switzerland
Monoclonal antibodies for use in research continue to be produced using hundreds of thousands of rodents. The main reason for this is the complexity of the in vitro method and the limited use of commercially available phage libraries. In this project a new combination of techniques will be examined (high-throughput sequencing and DNA synthesis) with which the procedure can be carried out at a much lower cost. A sufficiently complex phage library should be made available to research laboratories without any restrictions and phage selection should be possible using fewer experimental steps. The simplified procedure could also be carried out in non-specialized laboratories. As a result, the simplification of antibody phage selection could help achieve a breakthrough in the application of this in vitro method, the principle of which has already been known to researchers for a number of years.
Project 131-12

25th Anniversary Meeting of the Swiss Laboratory Animal Science Association and the 3R Research Foundation Switzerland (July 2012)
Refinement goes together with Replacement
On the occasion of its 25th Anniversary, the 3R Research Foundation is holding a joint meeting with the Swiss Laboratory Animal Science Association. This Continuing Education course will be held at the Technopark in Zurich on 19th and 20th November 2012. Over 40 speakers and lecturers from Europe including Switzerland, and from the U.S., have been invited. The papers to be presented at the sessions organised by the 3R Foundation will highlight progress in regard to the 3Rs. The European umbrella organisation of national consensus platforms for 3R alternatives (ecopa) and the Swiss Association of Toxicology (Swisstox) have been involved in putting together the programme for the meeting. Around 500 people are expected to attend.
Online registration
More information about this event | Program

Bacterial Meningitis: Investigating Injury and Regenerative Therapy in vitro (June 2012)
3R-Info-Bulletin 49
Bacterial meningitis (BM) causes brain injury in the dentate gyrus (DG) of the hippocampus, with bacterial components and the host organ's inflammatory reaction contributing jointly to the insult. The researcher has succeeded in differentiating neural stem cells and precursor cells at different stages of development and simulating in them the reaction to the damaging effect of bacterial meningitis. It is likely that compromised brain areas can be repaired by grafting suitable stem/progenitor cells into brain tissue. This process has been successfully carried out in cultured brain slices in vitro. Thanks to the in vitro methods developed by the researcher, it will be possible in the future to carry out indicative preliminary examinations that are necessary to identify appropriate cells for transplantation, for example. It would only be necessary to use laboratory animals for the final confirmation of the in vitro findings.
3R-Info Bulletin 49 | Project 103-06

Publication of Annual Report for 2011 (June 2012)
On 21 March 2012 the Administrative Board approved the Foun-dation’s Annual Report for 2011, which describes its activities during last year, as well as the financial statements for 2011. A total amount of Fr. 660,000 was paid out for research projects. Six new projects were approved and the final reports on eleven pro-jects were received.
Annual Report for 2011 | PDF version

A novel ex vivo mouse aorta perfusion model (February 2012)
3R-Info-Bulletin 48
includes a report on the completed project
Establishment of an organ ex-vivo tissue slice model for cardiovascular research, in particular for therapeutic atherosclerosis targeting
Prof. Patrick Hunziker, Clinic for Intensive Medicine, University of Basle, Switzerland
In this project, aorta tissue of transgenic (ApoE-/-) mice was extracted and cultured ex vivo. A method was developed for obtaining the tissue and its subsequent on-line observation under a fluorescence microscope. It was possible to identify and characterise the sclerotic sections of the walls of the aorta (plaques) following perfusion of the aorta with specific markers. The time taken for changes to the cells could also be determined. The results obtained corresponded to a great extent to findings from studies using ApoE-/- mice, which shows that many studies, for example for preselecting potential new medicines, could be carried out ex vivo.
3R-Info Bulletin 48 | Project 111-08
Informations for applicants and project managers

Deadlines

Principal areas for financial support

Instructions Concerning Project Outlines

Instructions for applicants

Form for Project Outlines (Word)

Application Form (Word)

Form for yearly reports (Word)

Guidelines for Awarding Research Grants

Addresses

Additional 3R news


European Consensus Platform for 3R Alternatives to Animal Experimentation


UK National Centre for the Replacement, Refinement and Reduction of Animals in Research


The global clearinghouse for information on alternatives to animal testing


Non-animal Methods for Toxicity Testing


The European Partnership for Alternative Approaches to Animal Testing



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