by Ben Sturgeon, BSc; BVM&S; Cert EP; MRCVS
Regenerative medicine technology in humans and in animals is advancing at a much faster pace than most of us realise. It has offered hope to thousands humans suffering from diseases and injuries that destroy and damage vital cells. In animals, much research has been focus on orthopaedic injuries in horses and dogs: bone fractures, arthritis and tendon and ligament injuries and there have been numerous clinical trials on stem cell therapy in these animals, importantly the results have been encouraging and their use has entered clinical practise.
What is Regenerative Medicine?
Regenerative medicine is the process of creating living, functional tissue to repair or replace tissue or organ function lost due to injury, disease, age or congenital defect. This field holds the promise of regenerating damaged tissue and organs in the body by simulating previously irreparable organs to heal themselves. Regenerative medicine can improve the quality of life by supporting and activating the animals natural healing process.
In horses previously untreatable joint disease and equine injuries have been addressed utilising regenerative techniques with vets using IRAP, PRP and stem cell therapies to manipulate then the body’s biological mechanisms to stimulate healing.
There is ongoing research for these therapies and new information is being generated primarily looking at longer term results. While the promise of such “cures” is very exciting for both vets and horse owners, it is important to understand the science behind each therapy in order to have an understanding of the processes involved and then a reasonable expectation for success.
IRAP stands for Interluekin-1 (IL-1) Receptor Antagonist Protein although often referred to as autologous conditioned serum. As many of you will have unfortunately experienced horses are highly susceptible to both acute musculoskeletal injuries as well as chronic osteoarthritis or degenerative joint disease with osteoarthritis being arguably the commonest cause of lameness. 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 repetative cycle of cartilage and joint damage resulting in on going 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 and multiple aliquots can be kept of indefinite use.
Platelet Rich Plasma (PRP)
PRP is another product that is derived from horse’s own blood. Platelets are laden 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 typically those released upon activation. These growth factors and others act synergistically to encourage access of healthy inflammatory and healing cells to the area of tissue injury with 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 is then used for treatment. PRP has been most commonly used to treat tendon and ligament injuries with the goal of treatment to accelerate and improve the quality of healing. Recently vets also have begun to use PRP intra-articular to treat osteoarthritis with encouraging results.
Stem Cell Therapy
Stem cell therapy is an exciting area of treatment for equine injuries. Although there is much we still need to learn, the research is encouraging. Current on-going 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: hematopoetic and mesenchymal. We are primarily concerned with mesenchymal stem cells (MSC) because they appear to have the best potential for regenerative medicine. These MSCs are found in bone marrow, fat, 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 for healing with younger stem cells possessing an increased ability to heal and regenerate tissue compared to adult stem cells. This is the reason behind the interest in storing umbilical cord blood in horses and many companies offering storage facilities for human umbilical blood.
In equine practice stem cells are commonly taken from bone marrow obtained from the sternum or the tuber coxae in the pelvis. This procedure is done under standing sedation and is relatively risk free and painless to the horse. Once the bone marrow has been harvested it is sent to a lab where it is cultured and expanded. The culture and expansion process takes approximately 3-4 weeks generating tens of millions of stem cells with an average treatment using between 10-25 million cells. The stem cells are then injected into the affected tendon, ligament or joint. Recently, stem cells have also been used to treat chronic laminitis cases with encouraging results. The multiple uses for stem cells have yet to be determined.
The second source of stem cells is fat although fat derived stem cells only contain 2-4% stem cells unless they are cultured and expanded. Research comparing bone marrow derived to fat derived stem cells indicate that bone marrow derived stem cells are superior to fat derived stem cells.
Whilst regenerative medicine is an on-going area of research, therapies such as IRAP, PRP and stem cell therapies offer the possibility of successful treatment of previously considered career-shortening or career-ending injuries.
First Published December 2013 Equi-Ads