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Sunday, September 19, 2021

More than man’s best friend

MONICA CHAN / AGGIE
MONICA CHAN / AGGIE

Veterinary researchers discuss the possibility of stem cell therapy in humans

Dogs and cats may soon become more than just their owners’ pets by giving their human companions an even greater gift: a chance for a healthier life. Doctors from the UC Davis School of Veterinary Medicine believe that because these animals are affected by problems such as heart disease, arthritis and cancer, they are favorable models that can be used to better understand and treat the same ailments in humans.

Dr. Dori Borjesson, a professor in the School of Veterinary Medicine and a clinical pathologist, studies how stem cells can modulate the immune system of afflicted animals.

Our primary question [is], ‘when you give stem cells to an animal, how do they work to change inflammation or immune response?’” Borjesson said. “There is a lot of evidence that suggests that [changing an animal’s immune system] is one of the ways [stem cells] work.”

Scientists are careful to point out that the research being done is very different than  “animal testing.” Animal testing involves infecting healthy rodents or other animals with a disease and then studying the effects of the disease on the animal. At the veterinary hospital, researchers study the success of treatments on patients that are already sick or otherwise compromised.

At UC Davis, animal patients are given a systemic administration of stem cells to reduce stomatitis, a severe chronic inflammation. Anti-inflammatory and regenerative fatty stem cells are extracted from the animals’ stomachs and reintroduced into the body intravenously.

Alternatively, patients with bone deformities can undergo surgery and receive artificial soft or hard tissue created with 3D printers. With protein regrowth therapy, this treatment has proven to be successful in animals. This has led scientists into researching whether the same therapies could be performed on humans.

Such research involves a collaboration among a diverse group of professionals, including veterinary scientists, doctors, cell biologists and biomedical engineers. According to Borjesson’s colleague Dr. Boaz Arzi, an assistant professor and oral surgeon, this is because the research is composed of two different processes. The first part involves tasks in the laboratory, including working with stem cells, doing blood work and engineering tissue. The second part of the research is the actual therapy itself, in which a patient either receives an injection or surgery from a clinician scientist.

“Collaborating is very inspiring,” Arzi said. “You have people from all sorts of disciplines working together and it’s very exciting — there’s no competition. People are on the same page. We are all working towards the same goal, and you learn from each other.”

Dr. Fernando Fierro, an assistant adjunct professor at the UC Davis School of Medicine, works with the same type of stem cells as Arzi and Borjesson, and conducts a trial with dogs afflicted with osteoarthritis. A fairly common disease in dogs and older humans, osteoarthritis affects weight-bearing joints and usually causes inflammation. If left untreated, it can cause more serious structural damage.

For this reason, the California Institute for Regenerative Medicine has granted more robust funding for researchers at UC Davis, who hope to eventually transfer their findings to human clinical trials. Fierro’s team works to develop a stem-cell based therapy in which they inject stem cells into the dogs to make the necessary joint repairs without serious side effects.

Fierro has been cautiously optimistic about the dogs’ chances of recovery, noting that all dogs have different manifestations of the disease and varying degrees of severity.

“I would not be surprised if the results turn out to be some dogs get better and others don’t,” Fierro said. “Some might have the disease because [they are] overweight and [suffer] more damage to the elbow because there’s too much weight on it. Others might be […] very old [or] have a genetic predisposition. But we will learn a lot and we will use that data not only to get the dogs better, but also as proof to move this forward to our clinical trials with humans.”

Fierro said that one of the toughest aspects of his research is making sure that the therapies they develop work consistently in a variety of situations. Although the stem cells have been proven safe, they have not shown the expected results, forcing Fierro’s team to come up with a second solution.

“The stem cells don’t stay that long,” Fierro said. “We put them in the animals and they normally last for only a few weeks and then they’re gone. This is good news from a safety point of view, but also may be a problem if they don’t make the repair in that window, then we may not see any efficacy.”

Fierro and his team are working on making a second generation of stem cells more powerful, while continuing to maintain safety and increase efficacy.

The safety of the clinical trials performed by UC Davis veterinarians have caused their work to be heralded by the scientific community. Arzi’s work has been featured in The New York Times, The Guardian and various veterinary science publications. Borjesson was awarded the 2014 Zoetis Excellence in Research Award for working to cure oral inflammatory diseases in cats.

According to Borjesson, the stem cell therapy used has shown minimal side effects. The stem cells that Borjesson and her team use are adult-derived mesenchymal stem cells which have been deemed safe even in human clinical trials. Hundreds of animal injections have shown no significant adverse reactions.

“There have been small reactions,” Borjesson said. “If you put stem cells in a joint, many animals will have some sort of inflammation around that joint for 24 hours. Some of our cats will also have a transfusion-like reaction if we inject too fast, but all you do then is slow down the injection and they are fine. Those are very small side effects.”

The minimal side effects give the most promise to these treatments someday being performed in humans. Borjesson and her colleagues hope to receive additional funding from the National Institute of Health and other organizations in order to build the quality and quantity of their research and produce optimal results. According to Fierro, scientists expect to translate these treatments into human clinical trials in as little as two to four years, depending on the funding they receive. They remain motivated by their aspirations to find a cure in any patient, whether canine, feline or human.

“In each and every case, when you get a cure, it is so exciting,” Arzi said. “When you get a patient who has had treatments for years and is suffering, and you’re able to cure that, nothing beats that feeling. We like to find the problems that medicine did not solve yet and find an innovative solution to it.”

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