Researchers are exploring improved ways to heal these notoriously complicated soft tissue structures
Oh, that limp. That shoulder drop that makes your heart drop. Maybe it was a stumble, a weird sidestep, or just one jump or mile too many on the wrong day or footing. But the verdict has fallen: Your trusty, ribbon-winning steed has a tendon or ligament injury. Just cancel your show season right now, because this is bad news. So bad, in fact, that it could be career-ending.
Why are sprains (ligament injuries) or strains (tendon injuries) so detrimental in horses? After all, people recover from these types of injuries all the time. Even top-level human athletes can go back to their previous levels of performance. While the composition of tendons and ligaments and their healing processes are similar across most mammals, the reason equine patients are different has to do with how they use these structures and, also, the impossibility of horses not using these structures while they heal.
Fortunately, scientists are making headway in dealing with tendon and ligament injuries in horses, giving veterinarians hope for ways to bring equine athletes back to their previous levels of activity. But first, let’s learn more about how these sophisticated structures function.
Matrices, Collagens, & Blood Supply
In the world of bodily tissues, tendons, which connect muscles to bones, and ligaments, which connect bones to bones, stand out for their unique structure. They’re both basically made of a fibrous matrix filled in with elastic structures and very few blood vessels. That’s why they bleed so little, says Bob Grisel, DVM, of the Atlanta Equine referral clinic, in Hoschton, Georgia.
He says the lack of blood supply also restricts the healing process because the body can’t easily transport growth factors and other healing aids via these vascular “roads” to the injured areas; these regions simply can’t get the same attention from the immune system as they would if they were in a more vascularized tissue … . As a result, tendons and ligaments tend to go through a long, slow, rather rudimentary healing process that’s often left unfinished, Grisel says.
Roger K. Smith, VetMB, PhD, DEO, FHEA, DECVS, FRCVS, professor of Equine Orthopaedics at the Royal Veterinary College’s Hawkshead campus, in Hatfield, U.K., focuses on tendon mechanics in his research. He tends to think it’s not a lack of blood supply—tendon actually has quite a good blood supply, he says, referring to yet-unpublished research—that impedes their healing but, rather, other factors.
Damaged tendon tissue isn’t replaced by the same kind of tissue it once was. The original tendon and ligament tissue develops from what scientists call Collagen 1, says Jan H. Spaas, PhD, DVM, former CEO at Global Stem Cell Technology (GST), now with Boehringer Ingelheim. Collagen 1 is strong, allowing for strenuous movement during exercise. But a naturally healing tendon or ligament replaces the damaged Collagen 1 with the weaker Collagen 3, which is poorly organized and more prone to re-injury.
Frequently referred to as scar tissue, that Collagen 3 in tendons and ligaments can keep horses from going back to their previous levels of activity, our sources explain, as can incomplete healing due to the body’s decision to discontinue the healing process after a while. The treatment goal, then, is to minimize Collagen 3 formation while promoting as much healing as possible—a real Catch 22 in the world of veterinary science.
So how do you keep an injured tendon or ligament on the mend, even when the body wants to stop the healing process? There’s an old trick for that, which has been around for decades, says Grisel. “You want to essentially fake the tissues into thinking they’ve been re-injured so they’ll program a new inflammatory response, without actually compromising the fibers with a real new injury,” he says.
Is he suggesting we want inflammation in that tendon or ligament? Actually, yes. Inflammation sends an inflow of healing products (interleukins and other blood-transported cells and proteins that initiate repair) to the damaged structure. “You want to get all the benefit of an injury without causing re-injury,” says Grisel.
Smith, however, takes a different approach. “We do not know too much about the role of inflammation in tendon repair, but it seems that tendon suffers ‘failed healing’ because of the persistence of inflammation, rather than its resolution,” he says. “Furthermore, more inflammation means more fibrosis (scarring), which we don’t want in superficial digital flexor tendon injuries, although (it) may be more acceptable in injuries of other tendons and ligaments which don’t need to stretch so much.”
Plenty of Ideas, A Few Results
Scientists have had a hard time making tissue think it’s re-injured. It’s not for lack of trying, though. Historically, some veterinarians have used counterirritation (chemical blistering or thermal “pinfiring”) to create external blisters on horses’ (particularly racehorses’) legs, to stimulate ligament and tendon healing, Grisel says.
Researchers concluded pinfiring is not an effective treatment for tendon injuries.
And since the 1980s veterinarians have aimed therapeutic ultrasound, light, cold lasers, infrared lasers, and magna waves at injuries that all essentially use vibration to signal the body that the tissue is injured, without actually injuring it. They’ve sought similar therapeutic effects from acupuncture, massage, and topical therapies during this time.
Grisel says that in his professional experience, these modalities typically are neither harmful nor curative. He hasn’t observed much difference between horses treated with these re-injury modalities and those that haven’t been. “Overall, it has been a little disappointing.”
But in many cases, he points out, these methods were implemented during the acute (immediate) phase of injury, when the inflammatory response was already in place. This is the phase when veterinarians should be trying to alleviate inflammation via modalities such as cold therapy.
Over the past two decades, veterinarians have added extracorporeal shock wave therapy (ESWT) to their treatment arsenal. They use it to help treat a variety of soft tissue injuries, including collateral ligament desmitis of the coffin joint, tendonitis, and tendon avulsions (tearing).
“The mechanisms of action of shock wave therapy have not been completely clarified, but several benefits have been suggested, including pain relief, induction of healing, and dissolution of mineralized areas in soft tissues,” says Smith.
Researchers have found shock wave to be particularly effective at returning horses to function from ligament injuries such as hind-limb proximal suspensory desmopathy (TheHorse.com/37077).
However, says Smith, “there is limited evidence for a role of ESWT in inducing repair. In my opinion, its role is in alleviating pain.”
Surgeries: Hit or Miss
In humans, as well as in some dogs, tendons and ligaments can be repaired with surgery. In fact, autograft surgeries (using the individual’s own tissue to replace a ruptured or injured ligament or tendon) have become commonplace even in top athletes, leading to full recovery. Human doctors have cruciate ligament (which stabilizes the knee joint) surgical repair down to an exact science these days, which involves taking a nearby tendon and attaching it to the knee where, over a period of months, it “transforms” into a new cruciate ligament. Essentially, the tendon then regenerates itself.
So why don’t these medical miracles exist for horses? To put it simply, it’s impossible to get a horse to lie in bed during the postoperative healing process, Grisel says. “Graft surgeries require full rest until the new tissue attaches, but in horses you really need a structure that’s ready to function almost immediately because these animals are constantly moving and accommodating weight-bearing loads.”
Some researchers have tried using a polypropylene mesh to augment and accelerate tendon repair. While this technique has shown promise for stabilizing displaced tendons, it has not been very effective at replacing torn or ruptured fibers. Thus, many of these surgeries failed as well, says Grisel. “There just wasn’t enough time to gain strength before the horses started tugging on it, and there were also (tissue) rejection issues,” he says. “Plus, additional scar tissue would form around the prosthesis, compromising eventual functionality.”
Researchers have recently seen better (anecdotal) results when combining mesh implantation with concurrent stem cell graftings, says Grisel.
Stem Cell Therapy’s Results
With the 21st century came the introduction of stem cell therapy into equine practice, with the initial idea being to “regenerate” healthy cells to replace injured tissue. With ligament and tendon injuries, that meant rebuilding those structures with tissue that’s as similar to native tissue as possible and less like scar tissue.
A stem cell is an immature and unspecialized cell that’s not programmed (differentiated) to be a particular kind of body cell (muscle, blood, skin, tendon, etc.). Embryonic stem cells harvested from a fetus before Day 8 of embryonic development can still form all the body’s cell types (they are pluripotent). Adult stem cells, on the other hand, harvested from tissues (anywhere from older than Day 8 of embryonic development through adult horses) are already committed to one group of tissue types (germ line) and are multipotent. For example, mesenchymal stem cells (MSCs) can be derived from many tissues in the body and can be used to treat a variety of tissues and have donor-tissue-specific tendencies.
Thus, it made sense to place these adult multipotent MSCs into injured tendons and ligaments and let them become healthy Collagen-1-producing cells for those structures, and, voila, create brand new tendon/ligament. Early studies in live horses showed that stem cells would grow into healthy Collagen-1-producing cells when placed into a healthy tendon and ligament environment, says Spaas.
In practice, however, a horse’s own stem cells (often collected from his umbilical cord blood at birth and then stored, or collected from his fat or bone marrow as an adult) ended up serving a different role entirely.
“Stem cells never perform as well as differentiated cells in synthesizing new tissue,” says Smith. “Current theories with more evidence are that these cells are not regenerative—instead they modulate (reduce) inflammation, and this appears to be their main mechanism of action.”
In other words, researchers originally hoped that stem cells would simply replace the cells in the target tissue (which can be done reliably in the laboratory but not the live horse). But, instead, it appears stem cells have a different role, helping direct the healing process of injured and damaged tissues, with the end product more like native tissue.
A New Generation of Regenerative Medicine
Many researchers, mainly in the United States and Europe, have been looking to produce a new generation of stem cell therapy. Spaas says his group has found it’s possible to use healthy donor cells, divided into large batches for reduced costs, and “predifferentiate” them in the laboratory—to “tell” them to become the right cells, prior to injection. He and colleagues have been researching this yet-unreleased off-the-shelf therapy, with encouraging results, and are awaiting their work’s publication in a peer-reviewed journal.
The next steps for stem cell research, in general, says Smith, involve:
- Better retention of stem cells in the horse’s body;
- Understanding of the effects of multiple dosing;
- Validating the effects of allogenic (coming from another horse, as in Spaas’ work) stem cell therapy; and
- Better understanding of inflammation’s role in tendon and ligament healing process, and how mesenchymal stem cells influence it.
Tendon and ligament injuries do heal on their own, and rest remains the best home treatment. Left-to-heal structures, however, are more prone to re-injury and likely to get re-injured. To preserve your horse’s performance future, you can turn toward treatments aimed at improving the healing process. And as researchers keep investigating ways to heal injured tendons and ligaments, we can remain optimistic that these cases will no longer be career-ending—only career-postponing.