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EQUINE HEALTH
ADVANTAGES OF STEM CELLS
Stem cells therapies are gaining interest because they have several advantages over other types of treatment. “Veterinarians have been using cell-based therapies in dogs for joint treatment. There are not a lot of good studies yet—but there are many dogs that receive preparations containing cells that seem to
help. Some of these are preparations with fast turnaround (stromal vascular fraction or bone marrow concentrate) where they use cells from the fat tissue or bone marrow in dogs. Others are culture expanded MSCs. Both autologous and allogeneic cells have been used. The results are all over the place; some animals seem to respond very well. Some dogs receive an injec- tion and are good for a year, but some do not respond. I think this has to do with the disease complex and also the fact that these new thera- pies are often reserved for the worst cases. Stem cells might not be used until the veterinarian has tried everything else—so it may or may not work in those cases,” he explains.
“This is typical; if veterinarians are not familiar with the therapy, they don’t want to do any harm and may reserve cell therapies for those last-ditch effort cases—and it is hard to judge efficacy in those cases. A person might realize they are safe (if the treatment doesn’t harm the patient) but it may be hard to judge the efficacy because the disease is already at such an end stage,” Koch says.
“There are now two cell products approved in Europe, for treating non-septic inflammatory joint pain in horses caused by synovitis and early OA. These are HorStem and Arti-Cell Forte. These products are both using culture expanded MSCs. HorStem (a product from Spain) utilizes cells from equine placental umbilical cord tissue, and Arti-Cell Forte isolates MSCs from the peripheral blood of adult horses. These two products are both approved for use in horses with joint pain due to early-stage synovitis. They are slightly different in formulation.
“HorStem contains only the cells (15 million stem cells) and Arti-Cell Forte is a combination product. It is often portrayed by the company as a stem cell product but is actually only 2 million MSCs, plus PRP (platelet rich plasma). So, with that product it’s a bit difficult to know if the perceived effect is due to the cells or the PRP,
or whether the two may have a synergistic effect working together. I haven’t seen any studies where the company treated horses with 2 mil- lion cells alone, the PRP alone, or the combina- tion, to compare or show that the combination was superior to either one alone. That would be interesting to know,” says Koch. Maybe a study like that will be done, now that these products are commercially available.
“A study at Cornell University investigated mesenchymal stem cells from horses in their
research animal model, in which they damaged the cartilage in the joints of research horses. Some of those joints got stem cells and some joints got just the injection vehicle/fluid with- out cells. The joints were all treated at the same time. In the follow-up, the researchers saw that the cartilage in the joints that received the cell formulation were much more preserved than the joints that did not get those cells.”
There was less cartilage damage in the joints that received the cells. “This is a step toward the concept of regeneration. This field has been called regenerative medicine, but
we have to be careful in this kind of think- ing because it implies that the therapies, we’re using are rolling the marble up the hill and back toward an earlier, healthier tissue state. I am not sure if that’s true,” he says.
“I am not sure if these therapies can turn a damaged joint into a less-damaged joint, but the study at Cornell indicates that maybe we can arrest the damage and prevent further damage. These are two very different situa- tions. We can maybe freeze the joint in time, and it won’t get worse. We might be able to have some degree of disease arrest and joint preservation, but that’s not the same as a joint being regenerated and looking more like a normal joint that never had injury.”
In equine tendon injuries there are many treatments that do more than arrest the damage, because there is some tissue healing. “Still, if you do histology on that tendon, you can see that it’s not normal, original tendon tissue. It’s enhanced repair. With tendons and ligaments, the tissue can repair itself and become somewhat elastic and strong again, compared to scar tissue,” says Koch.
“If a horse has a tendon injury and you simply leave it alone, it will form strong scar tissue, but the scar tissue is like a knot in a rubber band. The knot itself is strong, but the interface above and below the knot is weak. This is typically where re-injury occurs. The concern with a tendon injury is that it will happen again—and when it does, it’s almost always between the scar tissue and the normal tendon tissue. Some people would say the scar tissue is too strong, and not flexible; when the tendon needs to stretch, there’s no give. People think the reason that the risk of re-injury of tendons and ligaments after stem cell treat- ment is reduced by 50% is because the repaired tissue is more flexible and giving—functioning more like the original tendon,” he explains.
“This is great, but we still can’t call it regenerative. We don’t want to create false expectations. I am excited about the use of stem cells. I think they will prove to have a role to play, but we need realistic expectations. With joint disease, there are strong indications that these cells may be disease-modifying, and potentially arrest disease progression. But to
Horse being sedated prior to treatment with equine mesenchymal stomal cells.
determine this, we’d have to damage the joint, let the damage progress for a while and then treat some of the joints with the cells and some with the placebo. You’d examine the joints at that time, to have a base line, to then be able
to see later if the cells arrested the damage and preserved the cartilage at the damaged state or made it look better than it did at the time of treatment. If that were the case, then I would say it had some regenerative qualities, but those studies have not yet been done.”
It is exciting that two new products in Europe have been approved; he feels they will benefit horses. “One of those companies was acquired by Boehringer Ingelheim (a large international pharmaceutical company) last summer, stepping into this field of veteri- nary regenerative medicine. This is a boost for everyone, to know that this big company thinks stem cells and regenerative medicine have a role to play in veterinary medicine, going forward,” says Koch.
The resources and enthusiasm that come with that will direct more money into this field. “I think we will see this type of therapy become available. Some of the advantages of doing this in equine medicine is that joint injections are common; equine veterinarians are comfortable doing this. Small animal vet- erinarians are less comfortable injecting cat and dog joints; it’s more of a specialist treatment.”
There’s possibility now for more consis- tent disease management—maybe being able to use infrequent joint injections to keep a
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