Researching disease and developing medication in humans is made possible with the use of cell and tissue cultures—basically, the building blocks of experiments designed to understand specific disease mechanisms and how therapies act and react on a cellular level. This process is essential in creating new medications and vaccines and allows candidate therapeutics to be tested in tissues at a microscopic level before moving to clinical human trials.

However the process isn't as straightforward in veterinary medicine. Specifically, in equine medicine, drug trials and treatments are typically tested in live animal research herds, an incredibly expensive and long process.

But that's where Mimetico comes in. Their "horse-on-a-chip" technology aims to significantly decrease time and cost associated with pre-clinical trials, the stage that comes before testing in live animals, with the goal of shortening the timeline for veterinary drug approval.

"The problem in equine medicine is that we don't have relevant models that we can use in the lab to study a wide variety of disease. For human medicine, we can use mice and multiple cell culture models. But for equine science, those reagents don't exist," said Dr. Carrie Shaffer, CEO of Mimetico Biosciences and Assistant Professor in the Department of Veterinary Science at the University of Kentucky.

Mimetico is working to make those models possible, something that would drastically change equine medicine.

"With horses, we don't have all the intermediate models that exist for human medicine. New drug trials and treatment strategies have to be tested in research herds. It's incredibly expensive, and you may have to wait a year and a half to find a herd suitable for a pilot toxicity or dosing study," Dr. Shaffer said.

"What we've developed are multiple in vitro (in a test tube or culture dish) organ-like systems that can be used for preclinical analyses before candidate drugs are tested in a large research herd. We can do the majority of dosing, toxicity, and drug dynamics studies in the lab before we send it for field testing, so we are able to reduce animal experimentation significantly, as well as time and cost."

Mimetico started by working with Central Kentucky equine hospitals during the annual Thoroughbred foaling season, which takes place January through late spring. If a foal or other young horse had to be euthanized for humane reasons unrelated to the study (for example, severe injury or birth defect), Mimetico would process organ tissue from that animal to create their microscopic organ-like systems.

"We have essentially allowed euthanized foals to live on in the form of in vitro organ-like systems that we can generate in the lab and use for a variety of different studies," Dr. Shaffer said.

"We have developed methods to enrich tissue-specific stem cells, and we use those stem cells to make the organ model of interest. They're completely self-renewable and we biobanked the tissue so that years later, we can retrieve the tissue from euthanized foals and start generating organ-like systems from scratch. Because we have this huge and valuable equine resource in Kentucky, we can generate organ-like systems from diverse breeds."

During the 2019 foaling season, the Mimetico team decided to start with lung tissue from a euthanized foal. The results were astonishing.

"We thought it had a pretty low probability of working because we can't buy many off-the-shelf reagents for the horse," Dr. Shaffer said. "With human medicine, you can buy essentially anything you need for in vitro research—antibodies, media, growth factors—so we had to develop and formulate all of the growth conditions and culture models from scratch. It turned out to work exceptionally well, so we cryobanked the lung and trachea from that first foal."

From there, they developed liver, kidney, small intestine, and stomach organ-like models. Then they worked with another company to move these organ-like systems into microfluidic chip devices for studying multi-tissue interactions. This method allows further understanding of how disease and drugs interact in a living horse, since body organs function together in an animal and do not exist on their own.

"(With Mimetico) we can now perform research in the lab that we could never before because we no longer require live animals for most studies. We are able to study disease mechanisms in specific cell populations and understand tissue plasticity and the response to injury under laboratory conditions. This technology will really speed up drug development for the horse, and will also allow us to look at repurposing drugs that failed in human clinical trials to see if they have application in the horse," Dr. Shaffer said.

Going forward, Dr. Shaffer and her team aim to publish academic papers describing the technology, perform more research and development in the lab, and search for funding. She notes that participating in Launch Blue's UAccel program helped her chart a road map for Mimetico's future. While there's a lot of work ahead, the future seems bright as she sees a possibility to develop these organ-like systems from samples obtained from non-invasive procedures, like a nasal swab or urine sample.

"This technology is really moving towards personalized medicine for animals, because we're developing non-invasive methods for sample collection," she said. "With non-invasive methods, we can develop organ-like systems from an individual animal that can be used to make diagnostic or treatment decisions."

The future uses for Mimetico's technology are huge and have the potential to drastically change veterinary medicine.

"This technology can also be extrapolated to other species," Dr. Shaffer said. "That leap would require a lot research and development but this could move veterinary medicine as a whole into the same sphere as human medicine."

By: Erin Shea

Launch Blue nurtures promising startup founders and university innovators through intensive accelerator and incubator programs. Its funding partners are the University of Kentucky: Office of Technology Commercialization, KY Innovation, the U.S. Economic Development Administration, and the National Science Foundation.