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New project (December 2014)
Validation of a human stem-cell based pluripotency test using a bioreactor-based culturing system instead of a murine model to effect the development of embryoid bodies into teratomas
Prof. Christian de Geyter, University Hospital Basle, Department of Biomedicine, 4031 Basle, Switzerland
After stem cells from donor tissue have been isolated (or cultured) it must be checked whether they have maintained their typical capacity to differentiate into various types of tissue (pluripotency). According to international guidelines, such tests for pluripotency of stem cells are normally carried out using mice with a non-functional immune system.
The authors propose to develop a new bioreactor-based system which will enable researchers to examine the differentiation of stem cells into various types of tissue in vitro.
Project 142-14

Completion of a project (December 2014)
Antibody phage selection strategy for application in non-specialized laboratories
Prof. Dr. Christian Heinis, Laboratory of Therapeutic Peptides and Proteins, EPFL, Lausanne, Switzerland
Most antibodies used in research are still produced by immunizing animals. Prof. Heinis and his team succeeded in the development of an antibody scFv phage display library that may be distributed to laboratories free of charge and without any intellectual property (IP) constraints. From this library, antibodies to targets of choice can be isolated in vitro, omitting standard techniques based on animal immunization. In addition, they developed a phage display selection strategy with significantly fewer experimental steps that should facilitate the in vitro generation of affinity ligands by non-experts. The proposed method should replace animal experiments that are commonly performed to develop polyclonal and monoclonal antibodies.
Project 131-12

Genetic manipulation of the human airway epithelium – a paradigmatic system to study host responses to human respiratory viruses (November 2014)
3R-Info-Bulletin 53
The airway epithelium is the main port of entry for many respiratory pathogens and an important barrier to infection. Experimental systems that are suitable for studying basic virus-host interactions are scarce and are still preferentially performed in animal models. Prof. Thiel and his team succeeded to establish a unique in-vitro airway epithelial-cell culturing system that permits the molecular analysis of host-pathogen interactions at the port of entry of many respiratory pathogens.
3R-Info Bulletin 53 | Project 128-11

New project (October 2014)
In vitro alternatives to in vivo bioconcentration testing with fish: restricted to rainbow trout or broadly applicable?
Prof. Helmut Segner, University of Berne, Centre for Fish and Wildlife Health, 3012 Berne, Switzerland
Xenobiotic substances are chemical compounds that accumulate as foreign substances (e.g. toxins) in organisms where they are normally not found. According to OECD Guidelines (TG 305, Guidelines for Testing of Chemicals, Degradation and Accumulation), the potential risks of such substances must be tested on animals. A large number of animals are used for such tests.
The project leader has already developed a liver cell culture system using cells from trout, a cold-water fish, whereby the testing can be carried out in vitro (Project 108-07). The researchers now propose to adapt this system for liver cell cultures from carp, a warm-water fish, in order to enable the in vitro testing to be carried out in various other parts of the world.
Project 141-14

New project (October 2014)
Hydrocephalus simulator for testing active ventriculoperitoneal shunts
Dr. Marianne Schmid Daners, Zurich Federal Institute of Technology, Institute for Dynamic Systems and Control, 8092 Zurich, Switzerland
The present generation of valves and shunts used for treating hydrocephalus is out-of-date. Blockages often occur in the artificial drainage system for transferring excess cerebral fluid from the brain to the abdominal cavity. As a rule, the reliability of new products or systems is tested on larger animals.
In order to alleviate the need for such animal testing, a new platform will be developed consisting of a simulator which can be used for testing ventriculoperitoneal shunts in vitro.
Project 140-14

New project (October 2014)
An in vitro micro-vascular model mimicking the endothelial barrier
Dr. Marietta Herrmann, AO Research Institute Davos, 7270 Davos Platz, Switzerland
The walls of the blood vessels that are lined with endothelial cells, which in turn are covered with pericytes, control the transfer of substances (nutrients, gases such as oxygen, etc.) in both directions (from the blood to the tissue cells and vice versa). Cells also pass through this barrier, e.g. antibody-producing cells, and access the tissue from the blood to eliminate pathogenic organisms that have entered the system. As a rule, studies of the mechanisms whereby substances and cells pass through the barrier involve the use of laboratory animals, mainly transgenic mice.
The aim of this research project is to develop a new in vitro culture system for the blood vessel wall whereby such studies can be carried out in vitro.
Project 139-14

Publication of Annual Report for 2013 (June 2014)
On 6 May 2014 the Administrative Board approved the 2013 Annual Report on the Foundation's activities as well as the financial statements for 2013. A total of Fr. 568,479 was paid out for research projects. Four new projects were approved and three final project reports were submitted. Moreover, the Administrative Board decided on a major overhaul of the Administrative Board and the Evaluation Committee.
Annual Report for 2013 | PDF version

A new in-vitro approach to the study of brain tumours: an alternative to in-vivo experiments in animals (June 2014)
3R-Info-Bulletin 52
In humans, glioblastomas are the most common and most aggressive type of brain tumours. Animal experimentation as part of research into glioblastomas causes extreme suffering since it involves implanting a tumour in the brain of a mouse. Together with his research team at the University of Geneva, Dr. Olivier Preynat-Seauve has succeeded in developing a cell culture model whereby the interaction between the tumour cells and nerve tissue can be simulated. Through this model, experiments that cause considerable suffering to the mice should become superfluous.
3R-Info Bulletin 52 | Project 115-09

Completion of a project (May 2014)
In vitro fish hepatocytes as source of metabolic clearance data in alternative approaches for the reduction or replacement of in vivo bioaccumulation testing with fish
Prof. Helmut Segner, Centre for Fish and Wildlife Health, Vetsuisse Faculty, University of Berne, Switzerland
Numerous substances in daily use (cleaning fluids, cosmetics, medication, etc.) that are disposed of in waste water cannot be broken down naturally. Subsequently, they accumulate in various natural habitats a well as in animal species (bioaccumulation) with damaging effects on flora, fauna, the quality of our drinking water, etc. The problems caused by bioaccumulation are investigated using, among other things, trout. Prof. Segner and his team have succeeded in developing a new in-vitro testing method using liver cell cultures from these fish thus replacing testing in live animals.
Project 108-07

Completion of a project (May 2014)
Organotypic slice cultures derived from brains obtained from slaughterhouses as an in vitro alternative for the investigation of neuroinfectious diseases in ruminants
Prof. Anna Oevermann, Vetsuisse Faculty, University of Berne, Switzerland
Infections of the brain (or of the central nervous system), for example through bacteria (listeria), viruses (BSE) or active protein molecules (prions) normally lead to serious disease in humans or animals. So far, there is a lack of laboratory models, for example in vitro simulation, for researching such diseases. Prof. Oevermann has succeeded in developing a culture model for investigations in this area by using nerve tissue taken from animals obtained from slaughterhouses.
Project 116-09

Completion of a project (May 2014)
Development of an in vitro model from embryonic stem cells for identifying tissue inflammation as a reaction to implanted material
Prof. Maria Wartenberg, Department of Molecular Cardiology, University Clinic, Friedrich Schiller University, Jena, Germany
The development of new implant material for artificial hip joints, etc. involves, among other things, testing the rate of tolerance among recipients. Normally this is done using live animals. Prof. Wartenberg has succeeded in developing a tissue tolerance test using embryonic stem cells. This in vitro method provides valuable information as to potential tolerance in humans.
Project 117-09

Completion of a project (May 2014)
Nerve-cell mimicking liposomes as an in vitro alternative for demonstrating the potency of toxins with multistep pathways such as Botulinum neurotoxins (BoNT)
Dr. Oliver G. Weingart, Institute of Food Sciences, Nutrition and Health, Zurich Federal Institute of Technology, Switzerland
Botulinum neurotoxins are not only dangerous substances that are produced by bacteria in cases of infection and can lead to nerve paralysis, but are also used in a cosmetic preparation to eliminate wrinkles caused by ageing. Normally such neurotoxins are tested on laboratory animals. In this project, Dr. Weingart has achieved a major step towards developing a new in-vitro based efficacy test for these substances.
Project 125-11

Completion of a project (May 2014)
Model development and validation to investigate myeloid cell homeostasis
Dr. Charaf Benarafa, Theodor Kocher Institute, University of Berne, Switzerland
The blood's defence cells live for only a short time – a matter of hours – and for this reason many animals are required for research in this field. In order to replace these animals in the future, Dr. Benarafa and his team attempted to make such cells "immortal" so that many fewer or even no laboratory animals would need to be sacrificed. Unfortunately it was found that cells transformed in this way lose an important defence ability and certain other characteristics, with the result that they are no longer of use in research.
Project 126-11

Completion of a project (May 2014)
Genetic modification of the human airway epithelium – a paradigmatic system to study host responses to human respiratory viruses
Prof. Volker Thiel, Institute of Immunbiology, St. Gallen Cantonal Hospital, Switzerland
Many infectious diseases in humans start off in the airways, where germs manage to adhere to the airway epithelium and infect the victim's body (colds, influenza, etc.). Research in this field is based principally on animal experimentation. Prof. Thiel has succeeded in devising an in vitro epithelium cell model which will enable researchers to study the development of such human respiratory diseases in vitro.
Project 128-11

Completion of a project (May 2014)
Using a microfluidic chamber to study mitochondrial transport in PTEN and SOCS3 dependent axonal regeneration
Prof. Zhigang He, Children’s Hospital Boston, USA
Research into healing processes in damaged nerve fibers (axons) and testing of new substances for promoting such healing rely heavily on the use of laboratory animals. Prof. He and his team at the Boston Children's Hospital in the USA have succeeded in developing a new in-vitro system for investigating the early processes in the healing of such fibers using cell cultures.
Project 129-11

Completion of a project (May 2014)
Identification of predictive in vitro markers for hematopoietic stem cell function
Prof. Matthias P. Lutolf, Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, Lausanne Federal Institute of Technology, Switzerland
Human haematopoietic stem cells have been successfully used in medicine to treat leukaemia. Before the treatment can be given, however, many tests must be carried out to determine the stem cell characteritics and various other functions and abilities of the cells, which normally involves laboratory animals. Prof. Lutolf has succeeded in developing a new in-vitro method for obtaining this information whereby some of the testing can be done in vitro using new markers.
Project 132-12
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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