Veterinarians first used stem cells as a regenerative therapy in horses in 1995. Since then, scientists have learned a lot about stem cells and how they work, and the treatment is becoming more common for certain types of injuries. The field is rapidly evolving, though, and veterinary researchers have many more questions they hope to answer in their quest to help horses.
Lauren Schnabel, DVM, PhD, Dipl. ACVS, ACVSMR, is an associate professor of equine orthopedic surgery in the Department of Clinical Sciences at the North Carolina State College of Veterinary Medicine. She recently spoke at the 2020 Northeastern Association of Equine Practitioners Symposium, held virtually, where she shared the current use of stem cells in horses and the research leading us into the future.
Autologous vs. Allogeneic Stem Cells
Stem cells are cells that have two unique properties: the ability to self-renew, creating more new stem cells, and the potential to develop into many types of cells, such as muscle, blood cells, or bone.
The most-used stem cell in equine medicine is the mesenchymal stem cell (MSC), which originated from the cell’s mesoderm layer during embryonic development. The mesoderm gives rise to muscle and connective tissue, which means MSCs can differentiate into cells such as tenocytes, which are the basic units of the tendon.
In horses, adult MSCs are frequently harvested from bone marrow or adipose (fat) tissue in live animals.
“Adult MSCs are commonly used in veterinary medicine, and they are being used in human clinical trials,” Schnabel said. “They’re easy to use in that they can be patient-specific, or autologous. So we’re harvesting our patient’s own bone marrow or fat, and that’s advantageous for not having to worry about an immune reaction.”
When injected into a horse, stem cells can create an immune response in which the body deploys antibodies to kill the foreign invader. The chances of that happening increase when the MSCs are allogeneic, or genetically dissimilar because the donor was a different horse
Researchers are studying ways to use allogeneic stem cells safely and effectively, which would allow veterinarians to have a supply of ready-to-use stem cells on hand without having to harvest and culture MSCs for each horse.
“I do really believe that advancement of stem cell therapy is dependent upon practicality, safety, and efficacy, and I would love to have screened and banked cells for off-the-shelf therapy at the time of diagnosis, which would be allogeneic,” Schnabel said. “We know that genetic background can affect the cell proliferation and differentiation ability and that quantity and quality of MSCs decrease with advancing donor age. A lot of the population that we treat here clinically is older sport horses, so I’d love to have MSCs from young donor horses that we know are of good quality ready to go. My laboratory is focused on trying to manipulate the MSCs in vitro (in a lab) to make them safe to use in vivo (in the live horse) in an allogeneic way.”
Promising Results and Unanswered Questions
Most of the peer-reviewed, published studies to date have focused on using MSCs to treat tendon injuries. Tendon injuries can be debilitating for horses, because they are slow to heal and have a high rate of reinjury.
Schnabel cited research showing promising results with MSC therapy, particularly for superficial digital flexor tendon injuries. In one study a team of researchers followed horses for two years and noted a reduction in reinjury rates from 55% in the control group to 25% in horses treated with stem cells.
“What I always tell owners when we’re talking about stem cell use is it’s not that your horse is going to get back to work faster or have less time in rehab,” Schnabel said. “But they’re going to heal with tendon that is more normal and be less prone to reinjury, which is really critical.”
Research into treating equine meniscal tears (to the membrane between the stifle joint) have also shown promise, offering a higher return to work rate among horses treated with MSCs.
Still, Schnabel said, many questions remain unanswered.
“There’s a lot, unfortunately, that we still don’t know,” she said. “We really don’t know what our optimum stem cell number is. We also really don’t know the optimal stem cell type. Combination therapy is also a question mark. Should we be injecting with PRP (platelet rich plasma), or is another biologic better? And we just honestly don’t know. There seems to be some synergistic effect that can happen with the other biologics and rehabilitation modalities, but it is still a largely unexplored area.”
Schnabel is hoping to answer the question of when to treat injuries with research she is currently conducting. Current recommendations are to wait until the acute inflammatory phase is over before treating with MSCs. Schnabel is studying the cytokine (an inflammatory mediator) environment in the tendon to try to determine the optimal time to treat tendon injuries with stem cells.
“I think the real question here is, can we actually stimulate our stem cells to secrete factors that improve healing more if we inject them during this inflammatory phase? That’s to be explored, but I’m excited about this study,” she said.