Research into Osteogenesis Imperfecta – or brittle bone disease – has been conducted for years using laboratory animals such as mice, rats, horses, and goats. However, because these animals stress their bones differently than humans, the results are not always usable. Researchers from the University of Twente, Amsterdam UMC, and pharmaceutical company Azafaros are therefore working on an animal-free research model under the name OImpact.
With our support, the researchers can develop, test, and compare the model with previous studies. In doing so, they demonstrate that their animal-free model works at least as well as research using laboratory animals.
In conversation with Liliana Moreira Teixeira Leijten, researcher at the University of Twente. “Proteins are the building blocks of our body. And an important protein in the bones is called collagen,” Liliana explains. Our bones also consist of cells – osteoblasts. “If the osteoblasts are defective or produce too little collagen, the bone becomes fragile and can break easily.” Compare a bone to a house. Are the bricks laid neatly in a row with enough cement between them? Then the house is sturdy. But are the bricks laid haphazardly and is there too little cement? Then the house collapses at the first gust of wind. “That is the case for patients with brittle bone disease.”
Bone healing at the cellular level
10 to 15 babies are born with brittle bone disease every year. The disease has a major impact on the lives of patients. They break their bones quickly and often. And this is for their entire lives; there is no cure for it. Dancing, jumping, playing sports: things that are taken for granted by many people are lifelong dangers for these patients. Treatment with medication, surgery, or physiotherapy is intended to alleviate symptoms and limit complications. Over time, many of the bones of patients with this disease are reinforced with metal rods and fixed in place with screws and plates. They must also be constantly on their guard against new bone fractures. Liliana: “Research into brittle bone disease can and must be improved.” We actually do not yet fully understand how bone healing works at the cellular level in someone with brittle bone disease. If we did know that, we could treat them even better and more specifically. With the broken-bone-on-chip model, we can make significant strides in that direction.”
Human model in the lab
Researchers from Amsterdam UMC and the University of Twente have jointly developed a broken-bone-on-chip model. This allows them to accurately investigate how bone fracture healing works in the laboratory. The model works with a chip: a small plastic instrument that allows researchers to cultivate and study cells. A bone consists of a collection of cells and tissue: those cells and tissue are also found on the broken-bone-on-chip. As a result, it closely mimics the natural conditions of the human body. With the help of the chip, researchers can recreate the human cell structure within the bone in the laboratory. This provides insight into exactly what those cells do when a bone grows together. “This first model focused on research into bone fractures in healthy people. We are currently developing the model further to mimic the bones of people with brittle bones.”
The further development of the broken-bone-on-chip model is proceeding step by step. Liliana: “We collaborate with patient associations and surgeons from various hospitals. This is important, because it lets patients know that we are conducting this research. And they are more willing to donate tissue, for example, leftovers after surgery.” That material forms the basis of the broken-bone-on-chip model. By using cells from patients with brittle bone disease, the research results align better with reality.
A better view of bone diseases
A working broken-bone-on-chip model for research into brittle bone disease helps researchers understand how these patients’ bones heal after a fracture. And which treatments or medications help the bones recover better, resulting in fewer deformities. “An important partner in this research is Azafaros. This company knows a lot about manufacturing and developing medicines. As a result, the research aligns better with how new treatments are conceived, tested, and ultimately reach patients in practice.” At the same time, Liliana and her fellow researchers are looking ahead. This model can also serve as a starting point for other more common bone diseases. “Think, for example, of osteoporosis, a condition that affects many elderly people.”
Better results without animal testing
Ultimately, says Liliana, the goal of the research is twofold. To gain a better understanding of bone repair in bone diseases, so that doctors can help with proper bone healing through the right treatment. On the other hand, another goal is the introduction of a research model that better mimics bone repair processes in human patients. “Animal testing has been the standard for so long. And for lack of a better alternative, that is perhaps understandable. We have learned from those studies. But now the time has come to take a step further with new technologies.” Research involving animals is particularly painful and partly useless, Liliana explains. “Animals walk on four legs. They distribute their weight differently than humans. They move differently than we do. It is like comparing apples and pears.” Animals are also genetically different. Researchers therefore modify the DNA of laboratory animals to conduct research. But even so, the results of animal research into brittle bone disease can never be directly translated to the human situation.
The next step is to prove what we are actually already seeing: that this human-centered model provides a better picture of what happens in the human body, thereby rendering animal testing unnecessary. Liliana: “I hope that in a few years we will no longer use a single laboratory animal for research into brittle bone disease. And that with this model we show: good, human-centered research works perfectly well without laboratory animals. Together, we are changing the standard.”
About Proefdiervrij
We are committed to a world without animal testing. We work together with scientists, policymakers and companies to develop innovative research methods that do not use animals and better reflect human biology. By stimulating and funding animal-free innovations, we accelerate the transition to science without animal testing.
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