Cell Therapy for Robey Osteoarthritis in Horses TheStem Working Lines | Bob & Harlan Part II
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By Heather Thomas ..................................................................................................
tem cell therapy has been utilized in horses to help heal tendon, ligament and joint injuries for more than 25 years, and new uses are continually explored. These are mesenchymal stromal cells (MSCs) which are isolated from fetuses, foals or adult horses, as opposed to embryonic stem cells from embryos. The MSC stem cells can be isolated from almost any tissue but most commonly obtained from bone marrow, fat tissue and from the umbilical cord of newborn foals. The two main methods are use of the patient’s own cells (autologous cells) or cells from another horse (allogeneic cells). The advantages of using autologous cells is that they are not rejected by the patient’s immune system, and there are less regulations for use. Disadvantage of using autologous cells is that it takes 2 to 3 weeks to expand the cells prior to use, to get enough. This involves a two-step process requiring the horse to return for treatment--after initial sample collection. This may hamper optimal treatment time since an adequate number of cells are not readily available. Allogeneic cell have the advantage of being already available--with time to select and potentially enhance cell functions prior to use. The disadvantage is that cells from another horse are recognized by the patient’s immune system (and rejected) faster than autologous cells. Also the regulations are different; allogeneic cell product development is considered drug development A number of veterinarians, clinics and stem cell companies treated thousands of horses with stem cells for many years. They started by treating soft tissue injuries and then progressed to treating joints. Some people also treated laminitis with stem cells. There was such an expansion of stem cell therapy in veterinary medicine that the FDA became involved, to make sure it was regulated and that this kind of therapy wasn’t being used inappropriately. Use of stem cells was put on hold, and the FDA ruled that stem cells fell into the category of drug therapy, with all the regulations for bringing a new drug to market. It has been difficult to overcome this hurdle, since it takes years and a lot of money to do this. There was very little stem cell use in horses for a number of years. Today, most commercial strategies are focused on developing frozen allogeneic cell products. One approach is use of alloge-
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neic stem cells from umbilical cord blood that could be basically off-the-shelf/storable and given to any horse. Two products have been approved in Europe, and trials are underway in North America to get equine products approved here. Two trials are looking at use of stem cells for treating osteoarthritis (OA) in horses. There are still a number of conditions in horses and humans that are difficult to treat successfully; we don’t have good treatments and/or the treatments are not 100% successful. Osteoarthritis is one of those conditions. Dr. Thomas Koch (Department of Biomedical Sciences, Ontario Veterinary College) has been working with stem cells for many years and says the fact we don’t have good treatments for OA is reflected by the many different ways that horses with joint pain are being managed and treated. “There are many products being used for OA, and veterinarians have different preferences in treatment. This indicates that no one treatment has been shown to be superior. There is interesting data in humans and animals, however, showing that stem cells may be useful in treating some joint conditions,” he says. Koch is founder and CEO of eQcell, a company that is currently starting two trials using stem cells in equine synovitis and early stages of osteoarthritis--one at University of Guelph’s Ontario Veterinary College Equine Sports Medicine and Reproductive Centre, and the other trial at the University of California-Davis Veterinary Institute for Regenerative Cures (VIRC). The Canadian study in equine fetlock and carpal joint osteoarthritis is authorized by Health Canada’s Veterinary Drug Directorate and is the first stem cell trial in Canada for treatment of equine osteoarthritis. The U.S. study in fetlock osteoarthritis is being conducted under VIRC’s Investigational New Animal Drug (INAD) with the FDA. Stem cell therapy holds a lot of promise because it has several advantages over traditional pain medications like bute (which merely mask pain and has a narrow window of safety and can have damaging side effects) that can’t be legally used in competition. There are biologic products that can be injected into joints, like PRP (platelet rich plasma) or IRAP (interleukin receptor antagonist protein), and there are fewer regulations regarding their use (as opposed to stem cells). “But it’s hit or miss whether they work, depending on the individual horse,” says Koch. Steroids have also been used for treating OA, but there is controversy about using those in joints because they may damage the cartilage. Stem cells therapies are gaining interest because they have several advantages. “There are now two cell products approved in Europe, for treating inflammatory joint pain in horses caused by synovitis and early OA. These are HorStem and Arti-Cell Forte. They both use culture expanded MSCs. HorStem utilizes cells from equine placental umbilical cord tissue, and Arti-Cell Forte isolates MSCs from peripheral blood of adult horses. These two products are both approved for use in horses with joint pain due to early stage synovitis but are slightly different in formulation,” he says. “HorStem contains only the cells (15 million stem cells) and Arti-Cell Forte is a combination product. It actually has only