Regenerative therapy is a specialty of CCESIC as Dr. Vidal, Dr. Carpenter and Dr. Aristizabal have all been involved in research studies and published in the equine and human literature on the biology and application of stem cells. The most common regenerative products currently include IRAP, PRP and stem cell therapies. These products offer the possibility of successful treatment of previously life-threatening or career-ending injuries. Consult your veterinarian to determine if one of these treatments may be appropriate for your horse.
Stem Cell Therapy
Stem cell therapy has opened is a now very common regenerative therapy that may employ stem cells from various sources such as bone marrow and fat, dental connective tissue of newborn foals (VetGraft.com) and amniotic fluid.
- Stem cell therapy: Stem cell therapy is an exciting new area of treatment for equine injuries. Although there is much we still need to learn, early research is very encouraging. Current ongoing research will begin to offer answers and to shed some light on the best applications and techniques for the use of stem cell therapy. Stem cells are undifferentiated cells that have the ability to replicate and differentiate into a diverse range of cell types. These cell types include tendon, ligament, cartilage, muscle and bone. There are two basic types of stem cells, the hematopoetic stem cell (resides in bone marrow and in blood) and mesenchymal stem cell (resides in bone marrow and in tissues). Equine regenerative medicine primarily uses mesenchymal stem cells (MSC) as the premise in equine veterinary medicine is to primarily treat soft tissue and joint injuries. These MSCs are found in bone marrow, fat, dental connective tissue, umbilical cord blood and tissue, and many other organs throughout the body. The younger or more immature the stem cell, the more potential they may have. The younger stem cells have an increased ability to heal and regenerate tissue compared to the adult stem cells. This is the reason for the recent interest in storing umbilical cord blood in horses.
- Bone marrow-derived stem cells (…, …): In equine practice stem cells are commonly derived from bone marrow obtained from the sternum or the tuber coxae. Once the bone marrow has been obtained it is sent to a lab where it is cultured and expanded into millions of stem cells. The typical dose ranges from 10 to 25 million stem cells per treatment. The culture and expansion process takes approximately 3 weeks. The stem cells can then be injected into the affected tendon, ligament or joint.
- Fat-derived stem cells (VetStem, …): The second source of stem cells is fat. Fat derived stem cells only contain 2-4% stem cells unless they are cultured and expanded. Therefore adipose derived stromal fraction is the more appropriate term used to describe this therapy. One of the advantages of the fat-derived product is that immune response in joints and soft tissues are much rarer compared to the bone marrow derived stem cell product.
- PulpCyte® (VetGraft.com): A new product that recently has entered the market is called PulpCyte® (VetGraft.com) which is an allograft obtained from dental connective tissue of new born foals that have expired from natural causes such as birthing complications. The allografts are mechanically extracted without tissue processing such as none marrow-derived cells (cell culture) and fat-derived stem cells (fat tissue digestion), screen extensively for potential diseases and subsequently stored. A significant difference is that the PulpCyte® allograft contains not only stem cells but these cells are imbedded in a protein matrix which protects the viability of the cells. Unlike any other stem cell product the viability of this cell product is > 90% at the time of arrival in the clinic and the PulpCyte® product can be refrigerated for up to 10 days without significant loss of viability. The protein matrix contains native growth factors and anti-inflammatory proteins similar to PRP and IRAP but at much greater quantities. The PulpCyte® product has next day availability to veterinarians and is considerably cheaper than the bone marrow and fat-derived products.
- PRP is another product that is derived from your horse’s own blood. Platelets are loaded with numerous growth factors that are released upon platelet activation. Large amounts of transforming growth factor beta (TGF-?) and platelet derived growth factor and smaller amounts of insulin-like growth (IGF), epidermal growth factor (EGF) and TGF-? are released upon activation. These growth factors and others act synergistically to enhance access of healthy inflammatory cells to the area of tissue injury, formation of new blood vessels (angiogenesis), formation of new connective tissue (fibroplasia) and regeneration of skin (re-epithelialization).
- PRP can be obtained in a matter of minutes. There are currently a variety of PRP kits available. Usually a centrifuge is used to help concentrate the platelets into the plasma which then can be used for treatment. PRP has been most commonly used to treat tendon and ligament injuries. The goal of treatment is to accelerate and improve the quality of healing. Recently veterinarians have begun to use PRP intra-articular to treat osteoarthritis.
- IRAP stands for Interleukin-1 Receptor Antagonist Protein and recently is being referred to as autologous conditioned serum. Equine athletes are susceptible to musculoskeletal injuries and osteoarthritis or degenerative joint disease. Osteoarthritis is a common cause of lameness in horses. Clinical signs include lameness, joint swelling and inflammation. These signs are a result of cartilage damage within the joint and inflammation of the joint lining or synovitis. Joint trauma results in the release of inflammatory mediators such as IL-1 and other cytokines. These cytokines including IL-1 can lead to further cartilage damage causing a vicious cycle of cartilage and joint damage which result in joint inflammation and lameness.
- IRAP was developed to counteract IL-1 that is produced in the traumatized joint and to slow the progression of osteoarthritis. IRAP works by preventing IL-1 binding to the IL-1 receptors in the joint therefore blocking the damage and inflammation caused by IL-1.
- IRAP involves drawing approximately 50 mls of your horse’s blood into a specialized syringe which stimulates the production of the antagonist protein. The blood is incubated in the syringe for 24 hours. After incubation the blood is placed in a centrifuge and the plasma which is rich in the antagonist protein is separated from the blood cells in multiple syringes. IRAP is then injected into the joint once every 7-10 days for 3-5 treatments. Samples are stored in a -80 C freezer until use.
- There are currently two products on the market – IRAP and IRAP II. IRAP is from Dechra Pharmaceuticals and IRAP II is from Arthrex Vet Systems. Recent research has compared the 2 products and concluded that IRAP II has a modestly improved cytokine profile but both products produced a significant increase in interleukin-1 receptor antagonist. These 2 products have not been compared clinically to determine if there is a clinically significant difference between the 2 products.
- For other novel joint therapies please contact Dr. Vidal for further consultation.
Bisphosphonate Therapy (Tildren, Osphos, Zoledronate)
Application of Regenerative Medicine
The most common applications for Regenerative therapies in horses are currently soft tissue injuries (tendon’s and ligaments) and joints. With the development of new intravascular (especially intra-arterial) application techniques of stem cells, the treatment of laminitis and more inaccessible soft tissue injuries such as those within the hoof have become possible. Other therapies such as for skin or for eyes are either already available in form of grafts (e.g. applicable to the cornea of the equine eye) or currently under further development.