Regenerative Therapy For Equine Athletes

Lameness can frequently present as a performance-limiting condition among many equine athletes, where the primary cause may be attributed to one or several bone, joint, tendon, ligament and muscular injuries, and can be collectively referred to as ‘orthopaedic disease’.

Lameness may manifest as the result of an acute traumatic injury, for example a tendon laceration, or as the result of repetitive cyclic loading leading to degeneration of tissue, for example cartilage damage leading to osteoarthritis in a joint. With further advances in orthopaedic medicine, there are several biologic agents that can be used to modify inflammation and slow progression of the disease process, stimulate healing of the affected tissue/s, and improve the structural integrity of the repair tissue beyond that of typical scar tissue. All of these mechanisms are essential for providing an optimal outcome for a horse and increasing the chances of successfully returning to athletic performance. This article will cover the three major biologic agents and their regenerative properties currently available to Australian horses, and discuss their applications for different kinds of lameness conditions.

1.IRAP – ‘Interleukin-1 Receptor Antagonist Protein’

This biologic agent is derived from the horse’s own blood and is an effective treatment for joint disease and osteoarthritis in horses. The primary mode of action is to block the activity of Interleukin-1 (IL-1), which is responsible for releasing numerous inflammatory cytokines within the joint that cause further cartilage degradation and progression of osteoarthritis. Blood taken from the affected horse is incubated for 24 hours to stimulate the white blood cells to produce the therapeutic proteins. These proteins are concentrated in the serum, which is collected after 24 hours and can be frozen and stored for future use. This serum also contains additional growth factors that may play a role in reducing joint inflammation and stimulating tissue repair.

Advantages

• Good scientific evidence of disease modifying effects in an equine osteoarthritis model, and applications for treating soft tissue orthopaedic injury are showing promise.
• Single blood draw provides sufficient IRAP to medicate several joints and can be frozen and stored for up to 12 months for future use.
• Can obtain good clinical improvement in joints that have shown limited response to corticosteroid injections.
• Allows for more frequent joint medication if required without potential side effects of corticosteroid joint medication.
• Safe to use in young/old/metabolic horses where corticosteroid joint medication is not ideal.
• Effective treatment for restoring a healthy joint environment post-surgery.

Things To Consider

• Requires a 24-hour delay from the time of harvesting blood to treating the affected joint/structure.
• For advanced cases, best results are achieved when a series of three IRAP injections are performed 1-2 weeks apart.

2. PRP – ‘Platelet Rich Plasma’

Similar to IRAP, this is a blood-derived biologic agent. PRP acts to enhance tissue repair by increasing vascularization (blood supply), stimulating new connective tissue and regenerating dermal tissue (skin). For this reason PRP has primarily been used to stimulate healing of tendon and ligament injuries, wounds and non-healing fractures. Recent research has also evaluated PRP as a potential treatment for joint disease; the evidence for this is more extensive in human medicine, but is not as well established in horses. Blood is drawn from the horse and processed to remove the majority of red blood cells and concentrate the platelets in plasma component of the blood; these platelets release large amounts of several growth factors when activated. PRP can be processed and is immediately available for use with several preparation techniques available. The primary difference between kits is the concentration of platelets and white blood cells present in the plasma. Based on current research, a 4 – 6 fold increase in platelet concentration with a low white blood cell concentration is considered ideal for orthopaedic use.

Advantages

• Immediately available for on-site treatment of the affected region.
• Suitable for intra-lesional or peri-tendinous/ligamentous injection of tendon and ligament injuries.
• Can be used to treat non-healing wounds.
• Potential use as a joint medication, especially with concurrent soft tissue injury.

Things To Consider

• Variability in PRP product obtained from numerous kits available.
• Limited storage potential due to smaller volume of PRP obtained from each kit.
• Further research is required regarding the use of PRP to treat equine joint disease.

3. Stem Cells – ‘Mesenchymal Stromal Cells’

Stem cells are undifferentiated cells that have the capacity to replicate into multiple cell types that make up specific tissues. For orthopaedic use, mesenchymal stromal cells (MSCs) are the cell type of interest as they have the capacity to differentiate into tendon, ligament, muscle, cartilage and bone. MSCs can be found in various tissues in high concentrations, including bone marrow, umbilical tissue and fat; the younger the cells the more potential they have to heal and repair tissue. For the treatment of orthopaedic disease, stem cells can be grown from bone marrow harvested from hip or sternum, or from fat harvested from the around the tail head. There are two forms of commercially available MSCs; ‘autologous’ meaning the cells are harvested from the animal which is to be treated and grown in a lab, or ‘allogeneic’ meaning the cells are harvested from a different animal, grown and stored to be used on another animal when required. Due to the process of acquiring and growing the cells, there is considerable cost associated with stem cell therapy. The applications for these cells include the treatment of joint disease, tendon and ligament injuries, and laminitis with potential for multiple other uses. In these cases the goal of stem cell therapy is to produce the best possible repair tissue that has mechanical characteristics as close to the original tissue as possible.

Advantages

• Can be used to treat joint, tendon and ligament injuries.
• MSCs can signal other stem cells already existing within the body to congregate at the site of injury.
• MSCs have the ability to produce mechanically superior repair tissue.
• Allogeneic MSCs can be stored in liquid nitrogen and kept on-hand.
• Autologous stem cells can be grown and stored for future use as needed.
• Multiple routes of administration possible; intra-articular, intra-lesional, or regional perfusion.

Things To Consider

• Significant cost associated with acquiring and storing cells. MSCs should ideally be administered in the repair phase of tissue healing, usually 4-6 weeks post-injury when the acute inflammation has subsided.
• Waiting period (4 weeks) is necessary while autologous MSCs are grown.
• Some research indicates autologous MSCs are superior to allogeneic MSCs; however, harvesting and replicating these cells from the injured horse is very expensive and is not currently available in Australia.

These biologic agents offer veterinarians a greater capacity to treat career-ending injuries in horses, improve or restore soundness, and maintain quality of life. Due to their associated cost, accurate diagnosis of the injury/disease process is essential when your veterinarian is electing to use biologic agents instead of, or in conjunction with traditional therapies. Combining diagnostic analgesia (frequently employed as nerve or joint blocks) with the availability of digital x-rays and detailed ultrasound can allow excellent characterization of the injury and can also be used to monitor healing and response to therapy during rehabilitation. The field of equine orthopaedics and sports medicine is constantly growing as veterinarians search for better ways to help horses. Any questions regarding the information presented in this article can be directed to phil.manchon@sconeequine.com.au