Ученые Университета Осло создают банк клеток «супер-доноров» для лечения болезней по всей Европе

On the forearms of those working in the laboratory at the University of Oslo, one thing stands out: mysterious round or cross-shaped scars in the skin. Here, researchers need skin cells, and they themselves step up in the service of research. The skin cells are allowed to grow and multiply, and then the work begins to reprogramme them into so-called iPS cells, induced pluripotent stem cells. These are cells that can divide indefinitely and can give rise to all types of specialised cells in the body. They can, for example, become muscle, blood or nerve cells. "Cells produced from iPS cells are increasingly being used in trials on patients. The goal is that they can be used to treat many types of diseases where there is a need to repair or replace damaged cells, tissue and organs. Examples include Parkinson's disease, degenerative eye diseases, serious skin diseases, heart attacks and diabetes," explains professor Joel Glover. He is head of the Norwegian Core Facility for Human Pluripotent Stem Cells, which is based at the Institute of Basic Medical Sciences at the University of Oslo, and is affiliated with the Department of Immunology and Transfusion Medicine at Oslo University Hospital (OUS). Several bone-marrow donors have special cells The core facility is currently engaged in a very exciting collaboration with the Norwegian Bone Marrow Donor Registry and the Ex vivo Cell Laboratory at OUH. The Norwegian Bone Marrow Donor Registry has an overview of 39,000 people who have registered as bone marrow donors. Among these there are some who are regarded as "super donors". "These individuals have a genetic make-up that means the cells we produce from them can be used to treat a large proportion of the ethnically Norwegian population, and in fact a large share of the ethnically Scandinavian and Icelandic populations as well. We are establishing a biobank similar to a blood bank. The biobank will contain iPS cells that can be renewed. That means that when a super donor gives cells, we can establish stem cells that in principle 'last forever'," Glover explains. The project is called the Norwegian Biobank of iPS Cells for Clinical Application (NIBCA). "The task of the core facility is to quality-assure every step in the process, which is absolutely essential before procedures can be established at the Ex vivo Lab that produces cells for use in patients," says the professor. Stem cells to be used to treat eye patients One of the first diseases that iPS cells in NIBCA could be used for is an eye disease called macular degeneration, or age-related degeneration of the retina. Here, the innermost layer of the eye, the retinal pigment epithelium, deteriorates. This leads to the gradual breakdown of cells in the macula of the retina, making it difficult to read and to see faces. "We are collaborating with Goran Petrovski at the Department of Ophthalmology at OUS. He and his team has been working on producing retinal pigment epithelium from iPS cells, and has tested transplanting this into pigs. They have the protocols in place, which means that as soon as we have established iPS cells in NIBCA, the ophthalmologists can set about designing patient trials. The retinal pigment epithelium from the iPS cells will then be able to repair the damage in the retina," says Glover. But for this to go ahead, more funding is needed. The researchers are working hard to secure this. Approaching the goal of nine super donors As an initial goal, NIBCA aims to recruit nine super donors. Each of us has a specific mix of surface proteins on our cells. In super donors this mix is less varied. As a result, their cells are not perceived as so foreign by the immune system if they are transplanted into another person. "We have found that nine super donors will be able to cover the need for cells for more than half of the ethnic Norwegian population," the professor explains. Potential super donors must first consent to donate cells. The cells must undergo a strict regime of tests to ensure they can safely be used in patients. Among other things, they must be examined for changes in the genetic material that could increase the risk of cancer. So far, seven super donors have provided a small piece of skin. Once the skin sample has been taken, it is cut into small pieces. These fragments are placed in a container with liquid, with a glass placed on top to press them down. The skin cells then begin to grow out. The cells are harvested, and the work of reprogramming them begins. "During the autumn we expect to have the skin cells from the final two donors in place. We are coordinating our efforts with several other countries. Through this collaboration we can approach full coverage of cells for the population, not only in Norway, but across the whole of Europe," says Glover. Testing treatment for Parkinson's, epidermolysis bullosa and heart attacks In Sweden, researchers are testing treatment for Parkinson's disease using stem cells. iPS cells from NIBCA will be able to be included in this kind of treatment. The treatment involves generating cells that are precursors to dopamine-producing nerve cells, which are then transplanted into the affected region of the brain. The expectation is that these will continue to develop and replace the nerve cells that have degenerated. In the United States, iPS cells are being used to generate skin for patients with the severe genetic skin disease epidermolysis bullosa. Here, the genetic defect is corrected in the iPS cells so that new, healthy skin cells can be produced. "Colleagues in Portugal are now producing heart muscle cells from iPS cells in batches of up to 50 litres in special 'bioreactors'. They use these to form a piece of heart wall that can be placed as a 'patch' over an infarct," says Glover. According to the professor, such large-scale production is an exciting development. It opens up the possibility of producing cells that society may need urgently in the event of war or disasters, such as blood cells or skin cells. "With just a few bioreactors, we here in Norway could also produce litres of such cells in a relatively short time, genetically matched to a large proportion of the population," he says. Among the frontrunners in Europe The establishment of the NIBCA biobank has now progressed to the point where Norway is among the frontrunners in Europe, according to the professor. "We are actively collaborating with similar banks being established abroad, so that we can coordinate the recruitment of super donors. In this context, NIBCA will be very important, particularly for the population of the Nordic countries. But bringing NIBCA to fruition requires more funding," says Glover.