At UTOMIC we focus on enabeling translational research in key areas that will benefit both humans and animals. We believe in accelerating innovation through projects that connect One Medicine research and healthcare, and at the same time obviate the use of laboratory animals.
Veterinary researchers from Utrecht University and clinical researchers from various university medical centres have recently been working together on a number of promising One Medicine pilot projects aimed at helping human as well as veterinary patients suffering from a non-communicable disease. Here are a few examples:
In some forms of cancer, radiation (with a linear accelerator) is the only way to effectively combat cancer. Radiation (radiotherapy) is particularly important in cancer forms which cannot be removed or removed operatively.
A standard therapy with a linear accelerator in humans often consists of up to 35 radiation treatments. However, despite the effectiveness of the therapy, radiation treatment remains highly harmful to the patient (animal and human). In veterinary patients the number of treatments has been reduced significantly to 16 times in recent years, showing the same effectiveness with less side effects. On the basis of these findings, the number of radiation treatments in human radiotherapy has now also been reduced.
However, for veterinary patients, the burden of radiation treatment is still heavy, because each time they undergo radiation, they must be brought under anesthesia. That’s why researchers at the Faculty of Veterinary Medicine continue to work with colleagues at UMC Utrecht, on a way to further reduce the number of radiation treatments. Using the new UTOMIC linear accelerator, including advanced software made possible by our partners, our researchers can now aim the radiation more precisely and thus reduce the number of treatments from 16 to 10 per therapy. That way they hope to help animals with cancer even better.
Osteosarcoma is the most common and very aggressive type of bone cancer in children and young adults. Once the tumor is metastasized to the rest of the body, effective treatment becomes increasingly difficult. At present, the survival rate is only 13-30% 5 years after the diagnosis. Osteosarcoma also occurs in veterinary patients, especially dogs. In some dog breeds, prevalence can be up to 27 times higher than in humans.
To develop more effective treatment strategies, clinicians must first understand the nature and behaviour of the tumor, ideally using a Magnetic Resonance Imaging (MRI) scan, which makes it possible to assess the tumor in relation to the surrounding tissues. However, in human patients with osteosarcoma, chemotherapy treatments are started immediately after the diagnosis, even before surgery takes place, making (histopathological) MRI studies more difficult. In dogs, on the other hand, diagnostic imaging is always performed before any kind of treatment takes place. Innovative MRI methods for investigating the tumor in detail can be developed much more easily.
The scientific literature describes sufficient similarities between the etiology and prevalence of osteosarcoma in humans and animals to establish that there is a lot to gain from joining forces for both human doctors and veterinarians. In cooperation with the UMC Utrecht and the Princess Máxima Centrum, the Faculty of Veterinary Medicine has set up a study with 10 dogs with the diagnosis of osteosarcoma.
UTOMIC researchers hope to gain more insight into the tumor and the relationship with the surrounding structures through the use of MRI. Subsequently, they hope to expand their research and explore the immunological environment of osteosarcoma. In addition, they want to investigate the effectiveness of pharmacokinetics and pharmacodynamics of new immune therapies, for both humans and dogs.
Hip dysplasia is a common orthopedic condition in both humans and dogs and is characterized by a hip socket that doesn’t fully cover the ball portion of the upper part of the femur. Patients with hip dysplasia often develop osteoarthritis from the hip joint, resulting in a lot of pain, movement limitation and, as a result, a decrease in the quality of life.
Joint research by UMC Utrecht and the Faculty of Veterinary Medicine aims to demonstrate that a number of musculoskeletal diseases, such as hip dysplasia, can be successfully treated with personalized 3D-printed implants. Following on testing on cadavers, the study now aims to treat 25 dog patients with hip dysplasia at the Utrecht University Veterinary Hospital. Successful results will allow personalized 3D printing to be integrated into both veterinary and human medicine.
To produce an exact 3D model, the patient’s hip joint is mapped using computed tomography (CT), producing a 3D image of the skeleton and the deformity. The 3D image is then sent to a highly specialized software program, where the deviations in silico are corrected to develop a model of a personalized 3D implant. A first set of implants is printed from plastic, allowing the surgeon to simulate the operation and ensure that the desired fit is achieved. The final 3D implant is printed from titanium. Once sterilized, the implant can be applied to the patient.
The results of the treatments have so far exceeded all expectations. In a next phase, studies will focus on integrating the technique into human medicine.
Naturally occurring Cushing’s syndrome is one of the most common endocrine disorders in dogs and is associated with multisystem morbidity and clearly increased mortality. In the majority of cases (85%) it is caused by an ACTH-secreting pituitary adenoma (pituitary-dependent hypercortisolism; PDH). Current medical treatment of PDH is with trilostane, which inhibits cortisol production at the adrenal level. This means that the pituitary adenoma can continue to grow and induce space-occupying neurological signs. Pituitary-targeting drugs therefore represent an unmet clinical need.
Unfortunately, finding these drugs is hampered by the lack of suitable in vitro models that contain species-specific proliferating pituitary adenoma cells. We have recently established a novel culture protocol that successfully induces canine pituitary adenoma organoid formation in vitro. Organoids are miniature three-dimensional structures grown from stem cells, that closely resemble the tissue or tumor they originate from. With our newly established culture protocol, we can culture 3D canine pituitary organoids use them to determine the proliferation-inhibiting and ACTH-suppressive effects of potentially pituitary-targeting drugs.
We expect that the pituitary adenoma organoids will help us to reliably and efficiently identify the pituitary tumor-targeting drugs. Even more, as Cushing’s syndrome in dogs is much more common than in humans, our findings might be of importance to human medicine as well.
Every year around 4 million people are diagnosed with a malignant brain tumor. The average life expectancy is less than a year and the current treatment methods, such as surgery and radiotherapy, rarely lead to healing and are often accompanied by serious side effects.
In dog patients, brain tumors are regularly diagnosed, with similar prevalence, prognoses and treatment options as in human patients. Moreover, there are many similarities between the structure of the brain and the properties of tumors in humans and dogs.
In a joint research project, the Faculty of Veterinary Medicine and the Radboud University Medical Center in Nijmegen have developed a minimally invasive treatment method to treat brain tumors. With the help of MRI and CT, steerable needles inject radioactive holmium balls (‘microspheres’) into the tumor. The radiation levels in surrounding structures are then monitored using a SPECT camera.
With this minimally invasive treatment approach, a higher dose of radiation can be applied than conventional radiotherapy, without damaging the surrounding or healthy tissue, minimizing potential side effects.
Pheochromocytoma is a neuroendocrine tumor arising from chromaffin cells in the adrenal medulla. Most pheochromocytoma are biochemically functional, producing catecholamines such as norepinephrine and epinephrine. They induce typical clinical signs such as tachycardia, hypertension, arrhythmias, collapse and restlessness. They are the serious and life-threatening.
The preferred treatment for canine pheochromocytoma is adrenalectomy, as removing the causative tumor will reverse the high catecholamine‒related symptoms and prevent uncontrolled tumor growth. Unfortunately, however, this surgery is a high-risk procedure and can be performed only at specialized facilities. Moreover, in about half of the cases, the tumor is highly aggressive and has spread into the surrounding tissues by the time of diagnosis, preventing surgical removal.
If left untreated, pheochromocytoma can lead to catecholamine‐induced conditions such as hypertension and tachycardia, as well as tumor mass‒related consequences such as tumor rupture and abdominal bleeding. Given the current lack of an effective medical treatment, there is an urgent need for new, non-surgical therapeutic strategies
To assess the potential of new pheochromocytoma-targeted drugs before testing them in vivo, a reliable, stable, and species-specific in vitro system is needed. In the last decade, huge advancements in cell culture techniques have been made, leading to the development of so-called organoids. Organoids are miniature 3D structures grown from (cancer) stem cells, that consist of organ-specific cell types with spatial organizations and cell-cell interactions similar to the in vivo organ or tumor. Organoids are therefore able to recapitulate specific organ/tumor functions and growth mechanisms. They are a highly suitable model to perform in vitro, high-throughput drug screenings with no need to use laboratory animals.
In our laboratory, we are culturing the pheochromocytoma-derived organoids. They could provide a valuable in vitro model to study the effect of drugs on pheochromocytoma cells and would lead to the improvement of life of many dogs with a pheochromocytoma.
All UTOMIC research proposals are conducted after consultation with the Animal Welfare Body Utrecht to ensure optimal animal welfare and scientific quality.