Cornell university researchers work to develop new treatment approach
Mastitis remains the single most challenging infectious disease faced by dairy farmers across the world. Producers and herd managers rely on a series of approaches to control and treat mastitis, including genetic selection, environmental management, nutrition, and selective dry cow therapy. In combination with strict hygiene protocol and other treatments, such as the use of teat sealants, headway can be made. Yet, mastitis persists. For the most part, veterinarians and dairy farmers have relied on antibiotics to treat mastitis. While they do work, they do not repair the tissue damage caused by infection, which can lead to abnormal and decreased milk production. Amid rising resistance to antibiotics, it is ever more important to find new and novel solutions for treatment.
At the Baker Institute for Animal Health at Cornell University in New York, researchers Dr. Gerlinde Van de Walle and Dr. Daryl Nydam are working in collaboration with others to investigate the potential of using stem cell compounds to treat the devastating disease. The project received funding from the Foundation for Food and Agriculture Research (FFAR), non-profit organisation New York Farm Viability Institute (NYFVI) and animal health company Elanco. The project recently received $1.38 million to continue studies, about half of which came from FFAR. The research is still in its early stages, but the team hopes to prove that stem cell compounds do have the potential for treating mastitis.
In a recent interview, Van de Walle and Nydam explained their roles in the project and what they have learned so far. Following the completion of her PhD, Van de Walle accepted a job at Cornell University where she started research on the regenerative properties of stem cells and how they promote healing. As research progressed, she became more and more interested in secretions from the stem cells themselves. Previously it was thought that stem cells injected into injured tissue differentiate into whatever cell is needed to repair damage.
“But now it is generally accepted that it’s not so much the stem cell itself that will differentiate into a cell, but basically, the stem cell will secrete a wide variety of bioactive factors that will then work on the local injured environment and stimulate those injured cells to become better,” explained Van de Walle.
She and her colleagues have spent years trying to identify and understand the different bioactive factors secreted by stem cells. They now understand that the bioactive factors secreted by stem cells have the power to regenerate injured tissues. But further research shows that they also secrete bioactive factors that can kill bacteria.
A few years back, she and Nydam met up and began talking about his biggest challenge as a researcher and dairy veterinarian: mastitis.
“We just came up with this idea that this could be an improvement, if it works to what currently is available in the field, to treat mastitis,” said Van de Walle. “You would basically kill two birds with one stone.”
As a dairy veterinarian, Nydam knows the devastating impact of mastitis. He’s always looking for ways to better manage the disease in cases where dairy farmers have failed to prevent it.
“We always want to prevent it first, but sometimes we fail,” he said. “And the cure rates from standard antibiotics for many of the pathogens that we’re working on right now aren’t that great. Rarely does a cow recover back to her previous milk production, so killing two birds with one stone is very, very attractive.”
Following their first meeting, the two were able to secure Hatch funding from the US Department of Agriculture (USDA) to investigate the properties of the secretome, containing all the secreted factors, from mammosphere-derived cells (MDC), a cell population enriched in mammary stem and progenitor cells. Their study showed that the MDC secretome promotes angiogenesis, epithelial cell migration, and contains proteins associated with immunity and defense. They also found that MDC secretome remains effective after freezing and thawing, which further enhances its therapeutic potential. The results were presented at a National Mastitis Council meeting where they garnered obvious interest from the dairy and animal health community.
Continuing on that research, Van de Walle and Nydam are working to identify the bioactive factors that confer antimicrobial properties to kill bacteria. Working closely with Dr. Anja Sipka, they are also looking into how the bioactive factors of stem cells can modulate the immune response, which is a third important factor in mastitis, explained Van de Walle. Sipka is a Research Associate in the Department of Population Medicine and Diagnostic Sciences in the College of Veterinary Medicine at Cornell University. She works with bovine neutrophils and macrophages to see how the bioactive factors secreted by stem cells can stimulate these immune cells to increase phagocytosis of pathogens in order to become better at fighting pathogens by initiating a robust innate immune response.
In the next phase of the project, the team will work collaboratively with Elanco to do an in vivo proof of concept trial in dairy cows with experimentally-infected mastitis. That research will begin at Elanco facilities in Germany early next year. In controlled experiments, they will compare the results of cows treated with antibiotics to those treated with the bioactivity secreted factors from the stem cells. Because host-pathogen interactions differ, one limiting factor will be that they can only test one pathogen at a time. Their focus, for now, will be Staphylococcus aureus, but they’re interested in studying Klebsiella pneumoniae as well because of the severe epithelial damage it causes to the udder.
In vitro studies in the lab have shown promise, said Van de Walle. “If we expose primary immune cells, like macrophages and neutrophils, to bioactive factors secreted by stem cells, they are better at phagocytosis and killing bacteria,” she said.
“The long-term goal would be a natural product that could be an adjunct or even a replacement for antibiotics,” she added. “That in itself would be huge.”
Gerlinde Van de Walle is an Associate Professor in the Department of Microbiology and Immunology at the Baker Institute for Animal Health at Cornell University. Daryl Nydam is the Faculty Director at the Cornell Atkinson Center for Sustainability and Professor of Dairy Health and Management in the Department of Population Medicine and Diagnostic Sciences in the College of Veterinary Medicine at Cornell University.
Text: Melanie Epp | Pictures: Dr. Gerlinde Van de Walle and Dr. Daryl Nydam