Imagine walking into the barn after a long day at work, looking forward to a nice ride to help you unwind. You pull your horse out of the stall and onto crossties and start your normal grooming routine of brushing his coat and picking out his feet when you notice one of his legs is warm and swollen. What do you do? Swollen legs can be caused by a variety of ailments, from something like cellulitis (an infection of the connective tissue) which can be treated with antibiotics, to a much more serious situation such as a tendon or ligament tear.
Tendons and ligaments are made of bunches of connective tissue fibres, arranged longitudinally into larger bundles. These bundles are arranged together to form cable-like structures that are usually able to withstand the daily stretch and force of the horse’s movement. When the force or stretch becomes too great, however, injuries can occur.
All horses are susceptible to ligament and tendon injuries, irrespective of age, sex, or breed. Of course, horses that have athletic careers are at a higher risk of these kinds of injuries due to the extra force put on their legs every day.
If you find your horse with a warm, swollen leg, it is important to call your vet. If your vet cannot get out until the next day, he or she may recommend placing a poultice on the leg under stable bandages.
Once your vet arrives at the farm they will complete a physical and possibly a lameness exam. If they determine your horse could have a tendon or ligament lesion they will suggest an ultrasound to look at the soft tissue structures in the legs. Your vet will be able to identify any changes in the fibre pattern of the tendon or ligament in question. These changes can be mild (where just a few fibres are disrupted) to severe, which can be complete rupture of the tendons or ligaments in the leg. From there, your vet will outline a treatment protocol, which will always include a lot of stall rest. Because blood flow to tendons and ligaments is poor to begin with, and especially if it is compromised through injury, even though the body can create more connective tissue the process is slow and the fibres will not be organized into the original pattern they were before the injury. This means the structure isn’t as strong as the original tendon or ligament.
While stall rest is essential to healing, there are newer treatments that veterinarians are implementing to encourage timely healing of tendons and ligaments. These treatments use biologics from the horse, often in the form of stem cells, genes, or blood that undergoes special processing to activate particular molecules that encourage healing.
There are a few options when talking about regenerative medicine in regards to soft tissue injuries in horses.
Stem Cell Therapy
Stem cells are undifferentiated or immature cells that can transform to become different cell types within the body. Embryonic stem cells can differentiate to become any type of cell in the body, whereas adult stem cells are more limited. Mesenchymal stem cells are adult-derived and transform to become connective tissue. These stem cells are generally harvested from your horse’s sternum bone marrow. This is done standing and the area is locally anesthetized before a specialized needle is used to remove the marrow. The amount of stem cells obtained from the marrow is actually quite small; the rest of the fluid obtained is basically a derivative of blood. This fluid contains a wealth of growth factors beneficial for healing tendons and ligaments. The combination of the blood derivative and stem cells are then injected directly into the lesion of the tendon to promote healing.
Stem cells can also be derived from fat. Similar to collecting stem cells from bone marrow, your vet can anesthetize the skin and harvest the fat cells underneath it and send them to a lab for processing. The processed cells are then injected into the lesion.
One of the more common treatments for soft tissue injuries in legs is platelet-rich plasma, or PRP. Platelets are small disk-shaped cell fragments without a nucleus found in large numbers within the blood plasma that are involved in the clotting process that also contain a high number of growth factors. These growth factors act to allow healthy inflammatory cells to the area and promote good blood supply by encouraging growth of new blood vessels to the site of the injury.
PRP is derived from the patient’s own blood and is collected much like a simple blood draw, and therefore much less invasive than harvesting stem cells. The blood is then spun in a centrifuge where the plasma is separated from the actual red blood cells. The plasma is then further processed to isolate the platelets and the end result is PRP. Much like stem cells, PRP is injected into the lesion in question. Studies have shown that following a controlled return to exercise, the quality of the tendon material is better than in lesions not treated with PRP. The length of time to return to full work is also slightly decreased.
The most recent development in regenerative medicine is gene therapy – a therapeutic delivery of nucleic acid into a patient’s cells to treat disease or injury. In the case of tendon or ligament injury, scientists are using this technique to create a plasmid DNA which is involved in growing blood vessels and in the development of bone and connective tissue. This is then injected directly into the lesion. This very new idea is still being rigorously tested, but shows very promising results.
Results of a study published in 2017 led by Professor Albert Rizvanov, who is based at Kazan Federal University in Russia, showed that gene therapy used within two to three months after injury resulted in the full restoration of a severely-damaged suspensory ligament and superficial digital flexor tendon in two subject horses. The researchers used a combination of the equine-derived vascular endothelial growth factor gene (VEGF164) to trigger the growth of blood vessels, and bone morphogenetic protein 2 (BMP2) for the development of bone and cartilage, which were cloned into a single plasmid DNA. Both horses were walking and trotting within a couple of weeks and were back to full competitive soundness within two months.
Tendon and ligament injuries are a common problem in equine athletes. Thankfully, veterinarians now have tools that enable them to better diagnose and treat these injuries. Hopefully, with the continued advances in regenerative medicine, return-to-work times for horses with these injuries will drastically decrease and they will be able to have long, sound athletic careers.
What are Biologics?
Biologics are biological products including vaccines, blood and its components, tissues, allergenics (derived from molds, pollens, venom, hair, etc.), somatic (non-reproductive) cells, gene therapy, and recombinant therapeutic proteins isolated from humans, animals, or microorganisms. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living cells and tissues used to treat a variety of medical conditions for which no other treatments are available.
Unlike drugs that are chemically synthesized and have known structure, most biologics are complex and not easily identified. They also tend to be heat-sensitive and susceptible to microbial contamination; therefore, aggressive aseptic management is necessary throughout the manufacturing and handling procedure.