Grants 2006
A total of 1 260.000 SEK awarded in Grants from the Swedish Fund for Research without Animal Experiments in 2006.
1 260.000 SEK was divided between 12 different research projects. The recipients shortly describe their research below. Some of the grants are used for scholarships for PhD students. An additional 10 000 SEK has also been awarded in support of information projects.
Torbjörn Bengtsson and Magnus Grenegård , Avd. för Famakologi, Inst. för Medicin och Vård, Hälsouniversitetet, Linköping " In vitro studies of cell-cell interaction and inflammatory and mitogenic mechanisms in a human vascular model"
150 000 SEK
Atherosclerosis gives rise to serious cardiovascular complications and is the principal cause of morbidity and mortality in the industrialized world. Studies during the last decade emphasize that atherosclerosis is a chronic inflammatory fibroproliferative disease of the arterial wall.
To understand what leads to the fatal events of cardiovascular disease we have to search for suitable models of atherosclerosis involving the major components of the blood-vascular compartment.
This project aims to replace or limit the use of animal models by developing a dynamic in vitro model based on human vascular and blood cells and protein components, in order to study cellular and molecular processes related to atherosclerosis.
The project has a high priority in a new-started strategic research programme " Cardiovascular Inflammation Research Center " (CIRC) at Linköping University and the University Hospital in Linköping. A good human cell model would help us not only to understand the mechanisms of atherosclerosis but also to design and test different preventive, diagnostic and terapeutic approaches of cardiovascular disease.
Anna Forsby and Johanna Lilja, Department of neurochemistry and neurotoxicology, Stockholm university, 106 91 Stockholm, "Neuronal cell model for identification of mildly eye-irritating compounds" annaf@neurochem.su.se
100 000 SEK
The Draize’s eye irritation test has been used during decades for identification of irritating and tissue damaging chemicals. The test, which is performed on rabbits, is quite painful and the scientific value of the results from the test has been questioned. Therefore, extensive efforts to find alternative methods have resulted in several validation studies. These studies have generated alternatives to the Draize’s test for chemicals, which induce severe eye tissue damage (corrosion), but there is still no method that is able to identify chemicals, which only generate mild eye-irritation, e.g. smarting pain. Mild irritation occurs when specific pain-mediating receptors (nociceptors) are activated. We will therefore in this project develop neuronal cell clones, which express specific nociceptors, in order to investigate the possibility to use them for the identification of mild eye-irritating chemicals. If the neuronal clones fulfil the criteria, there is a good chance that the alternative test batteries will be significantly improved. Today, when the EU chemical test strategy proposes an extensive eye irritation screening programme by using the Draize’s test, an optimised alternative test battery can result in that thousands of rabbits will be saved from painful experiments.
Anna Forsby and Helena Gustafsson, Department of neurochemistry and neurotoxicology, Stockholm university, 106 91 Stockholm, "Neurotoxic mechanisms for acute, systemic toxicity studied in vitro"
annaf@neurochem.su.se
130 000 SEK
All chemicals have to be studied in an array of tests in order to assess their risk for humans or environment. According to present rules, most tests shall be performed on animals (mostly rats, mice and rabbits) but there are strong forces working for their replacement with safe alternatives, especially because the REACH proposal will result that the 30000 chemicals to be tested require approximately 10 million animals. The objectives of the project are to develop and evaluate methods for acute, systemic toxicity, i.e. measuring how much an animal or human can be exposed to a chemical at one time before it dies. Since many chemicals are toxic because they affect the nervous system in some way, our theory is that these effects can be monitored in cells originating from nervous tissue. Effects of narcotic and pharmaceutical drugs, pesticides and industrial chemicals will be studied on nerve stimulation, signal transmission and energy supply in our cell model. It is our hope that the methods are valid and predictable so they can be integrated in a large set of different tests that can estimate a whole organism’s response on chemical exposure.
Roland Grafström , Institute of Environmental Medicine, Karolinska Institutet: Culture of oral keratinocyte stem cells: gene expression and sensitivity to programmed cell death
roland.grafstrom@imm.ki.se
80 000 SEK
Parts of this grant was used for a scholarship for PhD Student Claudia Staab
The overall aim is study the growth of the stem cells underlying epithelial regeneration in oral mucosa. Culture methods will be established, including variants without serum, for assessment of gene expression. Profiling of transcript and proteins will be made to determine expression differences between stem cells and epithelial cells of higher maturity. The utilization of stem cells in biomedical research are likely to provide new alternatives to work with laboratory animals, including for cancer research.
Tiit Land, Dept. Neurochemistry and Neurotoxicology, Stockholm University: Iron regulation and iron-induced oxidative stress in Alzheimer’s disease
70 000 SEK
Iron is an essential nutrient required for all organisms, but iron metabolism and cellular iron uptake have to be balanced since the excess of free iron is toxic and damages essential biological components of cells. It is well known that a misregulation of cellular iron homeostasis, iron accumulation in specific regions of the brain and iron-induced oxidative stress are major pathogenic factors in several neurodegenerative diseases, including Alzheimer’s disease. The aim of this project is to study iron regulation and iron-induced oxidative stress in Alzheimer’s disease by using an in vitro cellular model instead of using animal models that are often used to study complex diseases at the molecular level. As a cellular model, we are using inducible gene expression systems in neuronal cells that express mutations coupled to familial Alzheimer’s disease. To study neurotoxic mechanisms of London familial Alzheimer’s disease-linked mutation, we are using synthetic peptides derived from amyloid precursor protein (APP) transmembrane region bearing the London mutation.Studies of endocrine disruptors in the human adrenocortical cell line (H295R)
Erik Ullerås and Agneta Oskarsson, Inst. för biomedicin och veterinär folkhälsovetenskap, SLU, Uppsala: Studies of endocrine disruptors in the human adrenocortical cell line (H295R)
100 000 SEK
Disruption of adrenal steroidogenesis has been demonstrated after treatment with a number of environmental pollutants and medical drugs. Adverse effects on adrenal function have several consequences, for example dimished capacity to cope with physical and psychological stress. The human adrenocortical carcinoma cell line H295R produces the three steroids, aldosterone, glucocorticoids and androgenic steroids, in a similar manner as in the normal human adrenal. The aim of the project is to characterize the gene regulation of the steroid synthesis in the H295R cell line. Furthermore, molecular mechanisms for some adrenotoxicants will be investigated. The H295R cell line has a potential to be developed into an in vitro test model for endocrine disruptors acting on adrenal steroidogenesis.
Johan Rönnelid and Linda Mathsson, Akademiska Sjukhuset, 751 85 Uppsala: Immune complex-mediated regulation of cytokine production in rheumatic diseases and cancer
johan.ronnelid@klinimm.uu.se
100 000 SEK
Antibodies produced by the immune system can aggregate into immune complexes. Such immune complexes composed of antibodies and substances from the body are essential in the pathogenesis of rheumatic disorders and may have importance in the regulation of the immune defence against tumours. Today basic research in both these areas utilizes substantial numbers of laboratory animals.
Our aim is to understand how immune complexes influence the production of cytokines, signal substances of the immune system. The work is entirely based on in vitro research on human tissues and blood. For these purposes we develop new sensitive laboratory techniques to detect immune complexes and their immunological effects on human cells in vitro. Important parts are e.g. to establish totally human cell culture conditions without addition of animal sera, and to develop sensitive techniques for the detection of cytokine production in vitro.
Camilla Svensson, Avd för toxikologi, Inst för farmaceutisk biovetenskap, Uppsala universitet: From stem cell to T cell in vitro-optimization and validation of a new method for studying immunotoxicity
150 000 SEK
The immune system is known to be extremely sensitive to chemical exposure. Chemically induced disturbances can for instance lead to an increased susceptibility to infections and cancer. In many cases these effects are the result of an interference with the development of T cells, a cell type with a key role in the immune system.
The aim with this project is to establish and validate a cell culture system for evaluating the effects of different compounds on the formation of human T cells. If successful, this model can become a powerful and animal-saving tool in the screening for potentially immunotoxic substances. In addition this model will simplify molecular studies on how immunotoxicity develops.
Ada Kolman and Cecilia Clemedson, Expertrådet: Use of human toxicity data for the evaluation of in vitro tests
150 000 SEK
Human toxicity data on different chemicals in our environment (drugs, industrial chemicals, herbicides etc) will be collected and analyzed with the purpose to evaluate in vitro data. Human data on acute toxicity and animal data (LD50 values) will be used as an important reference system, which may show that a combination of in vitro tests is enough successful to predict human toxicity. If the in vitro tests are as good as or better than the animal tests on predicting human toxicity of chemicals, the animal tests used today for acute toxicity testing could be replaced by in vitro tests.
Jan Grawé and Natalia Kotova, Cellanalyslabb, Rudbeckslaboratoriet, Uppsala universitet: The micronucleus test: from in vivo to in vitro. Towards an in vitro model for the study of chromosome damage in human bone marrow cells.
80 000 SEK
The numbers of laboratory animals used for risk estimation of chemicals has successively decreased. However, regarding their potential to induce damage on chromosomes, the in vitro test alternatives are not wholly
statisfactory. This can lead to that a relatively large use of animals for
this purpose in the extensive EU programme for risk assessment of chemicals (REACH).
A much used test for chromosome damage is the bone marrow micronucleus test. In the present project we aim to develop an in vitro test for the same purpose. The test will be based on human cells which are cultured in vitro, but but through special culture conditions are made to develop and react to chemicals in a similar manner as if they would be in the body.
Maria Backlund, Inst för Miljömedicin, Karolinska institutet: Development of a human neural stem cell line for the detection of reactive oxygen species as a predictive tool for developmental neurotoxicity.
80 000 SEK
Lately concerns have been raised as it has been observed that some environmental pollutants and drugs can cause impaired cognitive functions in children if their mother was exposed during pregnancy. It us unclear how these deficiencies occur, but oxidative stress is believed to be involved. The central nervous system is exceptionally vulnerable during development, and to mimic this situation we want to use a neural stem cell-line that can give raise to the different types of cells found in the brain. The project aims at developing a sensitive system for detection of oxidative stress in cells as well as to investigate if neurotoxic compounds influence differentiation processes in neural stem cells. Due to the complexity of the embryonic development, chemicals need to be passed through a series of alternative test systems for screening of toxic effects, and hopefully the neural stem cell model can become one of them.
Stellan Hjertén and Ákos Végvári, Inst. för naturvetenskaplig biokemi, BMC, Uppsala: Studies of artificial antibodies against proteins, viruses and bacteria
70 000 SEK
Antibodies (a special type of proteins) against a certain substance (antigen= are raised in experimental animals and are commercially available. These experiments are very painful when the antigens are toxic which, for instance, may be the case when new drugs are tested. Is it possible without animals to synthesize “antibodies”, which bind to an antigen as selectively as native antibodies do? We are developing such a method: The antigen is added to a solution which, after some minutes, is transformed to a gel. The antigen is washed away and a cavity forms the shape of which corresponds to that of the antigen. When a mixture of proteins, one of them being the antigen, is added to the gel only the antigen fits into the cavity and, therefore, binds to the gel. The number of experimental animals will be strongly reduced if this method will be widely used. Accordingly, there are strong reasons to improve the method.
InterNICHE: Information on alternatives in education
coordinator@interniche.org
10 000 SEK
InterNICHE gets a general support for it's activities. InterNICHE is a network of students, teachers, and animal campaigners that support progressive science teaching and the replacement of animal experiments by working with teachers to introduce alternatives, and with students to support freedom of conscience. The network also offers an Alternatives Loan System, a library of products available for free loan anywhere in the world, as well as literature, support and advice for teachers and students. www.interniche.org