How, when, and why to try stem cell therapy for common athletic injuries
Physically demanding careers, such as those of competitive sport horses, are inherently accompanied by injuries, whether sustained in training, competition, or an unfortunate pasture mishap. In some cases those injuries can be quite serious, resulting in long layups, lost training days, failure to return to previous athletic function, high re-injury rates, and early retirement … not to mention the economic losses associated with each. Not that long ago, training- and performance-related injury treatment was restricted to a few tried-and-true tricks, predominantly controlled exercise, cold hosing, and anti-inflammatory drugs.
“Over the course of the past decade or so, the field of rehabilitation has evolved dramatically and now encompasses an impressive array of modalities to help injured horses, including stem cell therapy,” says Lisa Fortier, DVM, PhD, Dipl. ACVS, professor of equine surgery at Cornell University and Cornell Ruffian Equine Specialists, in Ithaca, New York.
Indeed, rehabilitation is now its own specialty in veterinary medicine, with hundreds of veterinarians worldwide certified as American College of Veterinary Sports Medicine and Rehabilitation diplomates; more than 120 of these focus on horses.
In this article we’ll describe stem cell therapy and explain how veterinarians incorporate it into their rehabilitation arsenal. Specifically, we will look at what sport horse owners need to know about this therapy and when it might be useful.
Understanding Rehabilitation: Where Do Stem Cells Fit?
Rehabilitation is a remarkably vast and varied specialty. Examples of rehab modalities include:
- Exercise Controlled walking, limb and core exercises, swimming, treadmill;
- Thermal options Cool-water circulating devices, cryotherapy, cold-water hydrotherapy, heat application;
- Electrophysical techniques Extracorporeal shock wave therapy, transcutaneous nerve stimulation (TENS), neuromuscular electrical stimulation;
- Mechanical soft-tissue techniques Massage, stretching, chiropractic; and
- Biological therapies.
“It is this latter group of rehabilitation modalities, the biologic therapies, that encompasses stem cell therapy,” says Fortier. “Grouped together with platelet-rich plasma (PRP) and interleukin-1 receptor antagonist protein, more commonly referred to simply as IRAP, biologic therapies are among the more novel therapies included in rehabilitation programs.”
Scientists have conducted stem cell research predominantly on Thoroughbreds, and veterinarians use the therapies in the racing industry. The sport horse industry, however, seems to be playing things more conservatively, say our sources, and has not yet fully embraced these biologic therapies, particularly stem cells.
Take, for example, a recent survey of 305 equine sports medicine or rehabilitation veterinarians from the United States, Europe, and Canada. Their patients primarily competed in hunter/jumper, dressage, pleasure riding, Western riding, and eventing. The most common breeds used in those activities were Warmbloods, Thoroughbreds, and Quarter Horses.
One of the key findings was that veterinarians primarily used time-tested rehabilitation modalities to manage injured sport horses. The most commonly reported techniques were:
- Controlled hand-walking (used by 97.3% of survey respondents);
- Therapeutic shoeing (96.1%);
- Icing (95.2%); and
- Compression bandaging (89.25%);
In that same survey researchers found that platelet-rich plasma and IRAP were also quite popular rehabilitation modalities, with 86.5% and 81.4% of survey respondents reporting having used these techniques, respectively. Nonetheless, stem cell therapy ranked much lower, with only 62.7% and 36.6% of survey respondents reporting having used mesenchymal and adipose-derived stem cells, respectively (Wilson et al. 2018).
Indications for Stem Cell Therapy
That survey also showed that tendon and ligament injuries were by far the most common reasons for incorporating stem cell therapy. Other far distant indications for stem cell therapy included:
- Managing neck or back pain/injuries;
- Following arthroscopic surgeries and fracture repairs;
- Generalized “poor performance”; and
- Maintaining the horse’s current level of performance.
Kyla Ortved, DVM, PhD, an assistant professor of large animal surgery at the University of Pennsylvania’s New Bolton Center, in Kennett Square, confirms that tendon and ligament injuries are very common among sport horses. These are typically “overstrain” injuries, where the stress on those structures exceeds tissue strength.
“Certain injuries are more common in specific disciplines, and many of these are certainly amenable to stem cell therapy,” she says. “Common examples of these include superficial digital flexor tendinitis in racehorses, or proximal suspensory desmitis in dressage horses.”
Other less common indications for stem cells, with far less, if any, research supporting their safety and efficacy, include:
A Closer Look at Stem Cells and How They Work
There are four main types of stem cells; we’ve outlined them in the chart above. The ones we are primarily interested in are the mesenchymal stem cells (MSCs). These are a subclass of multipotent stem cells—meaning they can create different cell types—that veterinarians can easily obtain from multiple sources throughout the bodies of fetal/neonatal, young, or adult horses.
While it might seem like the goal of stem cells is to “become” new tendon or ligament cells (or whatever type of cell is needed to repair a certain injured tissue), researchers have disproven this myth.
“Stem cells actually function by controlling the cells and inflammatory molecules at the site of injury,” says Ortved.
So, instead of transforming into a tendon cell, or tenocyte, MSCs injected directly into a tendon injury release chemical mediators that recruit resident stem cells to the injured area. It is those stem cells that differentiate into tenocytes. In essence, MSCs don’t play the instruments but direct the orchestra.
“Injected stem cells also release anti-inflammatory compounds and mediators that promote the formation of new blood vessels, growth factors to help the new tendon tissue grow,” says Fortier. “Those mediators are thought to be at least partly responsible for the healing effects of biologics through their characteristic ability to promote healing. Examples of these bioactive growth factors include transforming growth factor β-1 (TGFβ-1), TGFβ-3, indoleamine 2,3-dioxygenase, prostaglandin E2 alpha, and platelet-derived growth factor.”
“The combination of these activities directed by injected stem cells promotes the natural regeneration of injured tissues,” adds Ortved. “This means the healed tissue more closely resembles native tissue, rather than weak scar tissue that forms during ‘natural’ healing. Helping minimize the development of scar tissue will decrease the chances of future reinjury.”
Taking Rehab Step by Step
Regardless of which combination of rehabilitation techniques you and your veterinarian ultimately select to manage injuries, generally your goal is to facilitate return to performance. This requires working closely with your horse’s rehab team to know which modality to use at what point during the recovery process.
“To garner the most benefit from rehabilitation, the first step is to pinpoint the underlying injury,” says Fortier. “Only once a firm diagnosis has been achieved can a rehabilitation plan be mapped out.”
When to use which rehabilitation technique depends on the exact nature of the injury, whether the goal at that point is pain reduction, restoring range of motion, contributing to tissue healing, and/or strengthening healing tissues. Even the veterinarian’s experience with biologics greatly impacts how each horse is treated.
As excited as you might be about the prospect of having stem cell technology at your fingertips, know that it’s not a magic bullet. Researchers recently reviewed the plights associated with obtaining, processing, transporting, and administering stem cells to horses so you can get the maximum bang for your buck (Barrachina et al., 2018). Here are some of the many factors your veterinarian considers when planning your horse’s biologic needs:
MSC therapy is expensive. To use autologous stem cells, which are collected from your horse, processed, and used to treat his own injury, your veterinarian must sedate the horse and collect and process bone marrow (or fat) according to rigid guidelines using specialized equipment and laboratories. The cost of the equipment, supplies, and time adds up.
2. Delayed patient treatment.
The process of using bone-marrow-derived autologous stem cells is time-consuming. This method requires several weeks of culture to acquire a sufficient number of stem cells for administration. It is possible, however, to inject a subset of concentrated bone marrow cells immediately after collecting the marrow, while the remainder of the sample is sent for culture. Further, veterinarians can use PRP in the interim so the horse is at least receiving some form of biologic therapy while awaiting the delivery of the cultured cells.
3. Consider allogeneic stem cells.
Another way to circumvent delayed treatment times is to use allogeneic stem cells. These are stem cells collected from a different horse ready to inject into the patient. The main concern with allogeneic stem cell usage, our sources say, is that the patient’s immune system will view them as “nonself,” similar to bacteria and viruses, and attack and destroy them. However, many horses with underlying medical conditions, such as pituitary pars intermedia dysfunction (equine Cushing’s disease), equine metabolic syndrome, or insulin dysregulation, cannot use their own stem cells because those cells aren’t considered healthy. Thus, veterinarians must rely on allogeneic cells instead (e.g., for managing laminitis).
4. There’s no guarantee.
As Barrachina et al. noted in their review of stem cell pros and cons, “Although MSCs may be a promising treatment for equine musculoskeletal injuries, it is important to highlight that their actual therapeutic potential still remains unclear and that there are still several gaps in the knowledge to be investigated.”
For example, some veterinarians use combinations of stem cells, PRP, and other rehabilitation modalities. Because of this wide array of treatment plans and because equine veterinarians implement and adapt their own protocols to best help each patient, collecting clear data and creating a recipe book for biologic therapy is challenging to say the least.
As mentioned, veterinarians have used stem cells predominantly for managing soft-tissue injuries in Thoroughbred racehorses. As such, researchers have generated data on their safety and efficacy in this population, including:
- In one study, 77-98% of Thoroughbreds with naturally occurring tendinopathy (tendon disease or injury) showed improvement on ultrasound examination following stem cell treatment. Further, the reinjury rate was less than 30%.
- For horses with naturally occurring osteoarthritis, 78% returned to work after treatment. For horses with meniscal injuries in the stifles (i.e., to the “pillows” of cartilage that cushion the impact between the femur and tibia inside the stifle joint), 76% returned to work.
Fortier has also had great success with stem cell therapy. She shares, for instance, a story about Pistol, a 3-year-old colt that arrived into her care with bone damage in his shoulder joint socket, prompting exploratory surgery.
During surgery Fortier found bone and cartilage damage suggesting Pistol jammed his leg and the ball hit the socket. At the end of surgery, she injected a bone marrow concentrate developed using a process derived in her own laboratory. The concentrate contains stem cells, anti-inflammatories, proteins, and growth factors that can help repair bone and cartilage to return the joint to normal. Pistol recovered from surgery and treatment uneventfully and has been doing well.
In her recently published comprehensive review of stem cell therapy, Ortved summarizes the benefits of stem cells and attests that this therapy leads to “improved repair of tendon and ligament lesions” in sport horses.
However, she reminds owners that in this unique group of athletes, “a tailored rehabilitation program, including controlled exercise and adjunctive treatments, is also key to success in cases of tendinitis and desmitis. The nature and severity of injury will dictate that individual horse’s tailored rehabilitation plan.”
As for other potential stem cell uses, we must wait for researchers to disclose what they’re learning as they explore the myriad applications.