Part 2 of 3
To read part 1 click here.
by Jessie Bengoa
This article is sponsored by Platinum Performance®
Article originally appeard here: https://www.platinumperformance.com/articles/connectivity
From injury prediction and prevention to treatment and rehabilitation, leading veterinarians are advancing the science of maintaining and healing tendons and ligaments in the horse.
Featuring Veterinarians Dr. Lisa Fortier, Dr. Carter Judy, Dr. Jackie Hill and Dr. Santiago Demierre
Regenerative Medicine Furthers Healing
Regenerative medicine, arguably more than any other advancement in the last several decades, has changed the shape of healing for soft tissue injury cases. The theory is simple yet profound at the same time — veterinarians use a horse’s own body to heal itself. There are generally two classifications of mesenchymal stem cells — autologous and allogeneic. Both have been widely researched, both are taken from an adult horse and not sourced from embryonic tissue, and both have distinct advantages and disadvantages. Dr. Doug Herthel, founder of both Alamo Pintado Equine Medical Center and Platinum Performance®, was an early pioneer in the use of autologous stem cells in thousands of cases beginning in 1995. The term “autologous” indicates that the cells being used to treat the horse were derived from either bone marrow or adipose (fat) tissue taken directly from that horse, with bone marrow-derived stem cells considered to be the optimal choice for potency and efficacy by many veterinarians. The second category of cells is classified as allogeneic or, in other words, cells taken from one horse, cultured, then used to treat another horse. While significant hope was placed in allogeneic stem cells for a period of time, due to the potential for these cells to be used on a broader scale as a drug, researchers and practitioners are now seeing that autologous stem cells are preferable. Autologous stem cells provide high efficacy and a lesser occurrence of side effects.
The use of stem cell therapy has only come about in the past 25 years, with veterinary medicine out-pacing human medicine in both the number and breadth of cases on which stem cell therapy has been used as a successful treatment. For many years both veterinarians and human physicians and researchers knew the efficacy of stem cell therapy but were at a bit of a loss as to how exactly stem cells behaved within the body. Why were they so effective? At first it was believed that stem cells, when placed in a tendon, for instance, would create new tendon material. Today, we know that is, in fact, not the case. “How stem cells work is through what they secrete,” explains Dr. Fortier. “They pinch off little vesicles called secretome. It’s that secretome that then provides growth factors and draws more of the local stem cells surrounding the injury into the actual injury site.” Although it sounds futuristic, there are companies that today sell secretome as a standalone treatment. To accomplish this, stem cells are grown in a laboratory setting, then the secretions from the cells’ surface are harvested, including microvesicles that are filled with growth factors and chemokines. “In this case, we don’t even need the live stem cells, we just need what the cell is producing,” explains Dr. Fortier of the secretome approach. “This gives practitioners an even clearer advantage because they will eventually be able to deliver this material patient-side. Secretome will be available like a steroid in an OTC [over-the-counter] capacity, and we won’t have to worry about immune rejection or even a bone marrow draw and the three weeks it currently takes to culture cells.”
Regenerative medicine is a bright area in both veterinary and human medicine that Dr. Fortier knows well. “Perhaps one of the most important things we have learned more recently is how to grow these cells so that we don’t incite inflammation,” says Dr. Fortier. “One of the common ways that you feed cells while growing them in a laboratory is with fetal bovine serum. We now know that the horse’s body recognizes that foreign serum and mounts an immune response. The clinical significance of that is still a bit unclear, but Dr. Ashley Watts at Texas A&M is leading the charge in discovering that we should culture these cells in either no serum at all or by using the horse’s own serum itself.”
A primary advantage of regenerative medicine is that, when paired with quick and accurate diagnosis, this type of therapy can begin immediately, interrupting the inflammatory cycle early, decreasing inflammation and intervening in the healing cascade well before the remodeling phase. This sets the stage for a more successful outcome concerning soft tissue injuries. Veterinarians at select facilities have the ability to aspirate bone marrow on the standing horse, then centrifuge it down to get “the good stuff” known as bone marrow concentrate. In more technical terms, bone marrow concentrate is the portion of the anticoagulated bone marrow sample that includes leukocytes, platelets and growth factors, among other things, with the red blood cells and other undesirable aspects separated out by the centrifuging process. Bone marrow concentrate can be re-injected to the injury site less than one hour after bone marrow was first aspirated, allowing for veterinarians to provide a near-immediate treatment option while they wait for cells to culture, a process that takes up to three weeks to accomplish for the first re-treatment. “We know that it’s critical to get to lesions early. We are already starting to fall behind if we wait and do nothing until the stem cells are cultured for re-treatments. At the minimum that animal should have corrective shoeing, proper nutritional intervention and active rehab, then perhaps some other modalities like PRP, IRAP or Shockwave, amongst others,” says Dr. Fortier.
“We know that it’s critical to get to lesions early. We are already starting to fall behind if we wait and do nothing until the stem cells are cultured for re-treatments. At the minimum that animal should have corrective shoeing, proper nutritional intervention and active rehab, then perhaps some other modalities like PRP, IRAP or Shockwave, amongst others..”
— Dr. Lisa Fortier, A Boarded Surgeon and Highly Respected Researcher at the Cornell College of Veterinary Medicine
PRP, IRAP & Pro-Stride
In contrast to re-injecting bone marrow concentrate while waiting for stem cells to culture, tools such as Platelet Rich Plasma (PRP), Pro-Stride® (Autologous Protein Solution Device) and Interleukin-1 Receptor Antagonist Protein (IRAP) can be used to attain an immediate effect as well. PRP uses a concentration of the horse’s platelets in the form of blood plasma to bring growth factors to the injury site and begin the healing process. “PRP can help decrease some of that inflammation and prevent some of the break down,” explains Dr. Hill. In contrast to PRP, IRAP is generally specific to joints, though some veterinarians rely on this treatment for inflamed suspensory ligaments. IRAP begins with a horse’s own blood, which is then incubated with specific glass beads to increase the amount of naturally occurring IRAP present. The mixture is then administered by an intra-articular injection with the goal of blocking interleukin-1, a major inflammatory component released by the body in the event of an injury. “IRAP is mainly an anti-inflammatory for the joint but also has some other important factors and components. I have seen IRAP be very beneficial for some horses with a mild cartilage injury as well, and it’s a better option than using steroids for long-term healing,” says Dr. Hill. In addition to PRP and IRAP is a device that produces a combination of the benefits of both therapies. Pro-Stride® is a proprietary dual-device system that begins with the horse’s own blood and within 20 minutes is able to produce a concentrated solution of cells, platelets, growth factors and anti-inflammatory proteins (including IRAP) that is then administered by intra-articular injection. Interestingly, bone marrow concentrate also contains very high concentrations of IRAP.
Horse owners and veterinarians are often left to decide the best course of treatment, choosing between stem cell therapy, PRP, Pro-Stride® and IRAP based off of the horse’s individual case, severity of the injury and financial considerations of each treatment option. “From a purely medical standpoint, stem cells have been shown to have the best ability to both enhance healing and reduce inflammation. They would be my first choice,” says Dr. Hill. “At the same time, stem cells are a larger financial investment for the owner, and practically, that has to be taken into consideration. This is where things like PRP come in as a viable option. My optimal recommendation when I see a horse with a new tear in a suspensory or superficial digital flexor tendon is to immediately put PRP in there, then collect bone marrow and culture cells to inject a few weeks down the road.”
“We know that with both the deep soft tissue injuries and arthritis there is a large inflammatory component — an immune-mediated inflammatory component. We often think of them as purely degenerative diseases, but they aren’t simply degenerative. There is a very important immune system contribution, especially in the early phases.”
— Dr. Lisa Fortier, A Boarded Surgeon and Highly Respected Researcher at the Cornell College of Veterinary Medicine
The Role of Inflammation and Oxidative Stress
Inflammation and oxidative stress not only play a vital role in the healing process concerning soft tissue injuries, but perhaps of greater importance, they can increase a horse’s risk of injury in the first place. A horse in a managed state of inflammation will be more capable of handling minor insults to the tendons and ligaments without becoming clinical. In contrast, a horse in an unmanaged state of inflammation will be predisposed to both soft tissue injury and joint disease, such as arthritis. A horse’s level of inflammation can be influenced by several factors, including its environment and training, but diet has been shown to be amongst the greatest determinants of whether a horse’s inflammation is kept at a managed, healthy level or goes unchecked.
Much like inflammation, a horse’s level of oxidative stress can make them more prone to injury and disease. Oxidative stress is a direct cause of cellular aging and is the body’s response to excessive free radical damage, which can be the result of rigorous training, environmental pollutants and a diet high in rancid fats and feeds. “Like in every aspect of life, everything is about balance,” says Dr. Demierre. “Inflammation and oxidative stress are responses from the body and, in certain amounts and for short periods of time, they can even be beneficial for the normal function of the body’s biological systems. When unregulated, however, they can, and usually do, become detrimental.” Dr. Fortier agrees, “We know that with both the deep soft tissue injuries and arthritis there is a large inflammatory component — an immune-mediated inflammatory component. We often think of them as purely degenerative diseases, but they aren’t simply degenerative; there is a very important immune system contribution, especially in the early phases. There’s a large portion of T cells and macrophages that are involved in the propagation of disease whether it’s an early tendon injury or arthritis,” she explains. “Understanding what’s happening in the very beginning allows us to create windows of opportunity for therapeutic intervention. One of the biggest things that we are finally starting to appreciate is that we have to treat these injuries early before scar tissue is set up.”
While inflammation and oxidative stress may play a significant role in a horse’s risk for both injury and disease, they are factors that can be prevented and also treated with the right intervention. Diet, therapeutic nutrition, proper conditioning and aggressive and early treatment after injury can all influence a horse’s inflammatory state, chance of injury, rate of recovery and risk of re-injury.
Changing Outcomes with Rehabilitation
Undoubtedly one of the most significant factors in successfully treating soft tissue injuries, aside from regenerative therapies, is the exponential gains seen in the science of rehabilitation. Veterinary-directed rehabilitation has surged forward in recent years with the advent of new technology and techniques, as well as the founding of the American College of Veterinary Sports Medicine and Rehabilitation. Veterinarians and surgeons alike were previously frustrated that they would treat a horse or operate on a soft tissue injury only to send the horse home to be confined to a stall with no active rehabilitation plan. This approach differed greatly from human medicine, where physical therapy is a mainstay in the recovery process. “We don’t just stick horses in box stalls for 4 to 6 months anymore,” says Dr. Fortier. Rehabilitation and active rehab go so much further than simply controlled forms of exercise, but now include extremely effective modalities and a solid place for therapeutic nutrition. “Modalities like Shockwave therapy, laser therapy, therapeutic nutrition, proper farrier application and regenerative medicine are all key components,” says Dr. Fortier. “All of these things combined have increased our chances of not only getting the horse back to performance but sustaining performance. I tell my clients that they have to be committed to the rehab. It’s a least half of the equation in terms of the horse’s chance of recovery.”
Veterinary-directed rehabilitation has surged forward in recent years with the advent of new technology and techniques, as well as the founding of the American College of Veterinary Sports Medicine and Rehabilitation.
Come back next week for part 3.