Horse owners and veterinary practitioners are increasingly considering stem cells as an alternative treatment option - for problems such as tendon and ligament injuries, where standard veterinary treatments are not effective. This is particularly the case for high-value sport horses. And because the use of cell therapies in animals sits outside of the strict regulatory frameworks for human medicines, veterinary stem cell companies have proliferated, selling treatments that have yet to be properly tested.
Owners of high-value sport horses are increasingly turning to stem cell therapies to treat tendon, ligament and cartilage injuries.
Stem cell treatments in horses primarily use mesenchymal stem cells (MSCs), stem cells that differentiate into cells that form bone, tendon, fat and cartilage.
MSC treatments typically involve injecting MSCs from the bone or fat of a horse into areas with damaged tendons or cartilage.
Some experimental studies have shown positive results, but many stem cell treatments offered by companies have not been proven to be safe or to work at all.
MSCs in bone marrow and fat are quite scarce, making it difficult to get enough cells for treatments. Researchers wish to develop alternative ways to get MSCs more quickly, including using MSCs from donor horses or making them from embryonic stem cells and/or induced pluripotent stem cells (iPSCs).
More research is needed to establish that MSC treatments for horses are safe and effective. Most studies supporting the use of MSCs to treat horse injuries look at a small number of horses, use vastly differing methods, don’t have treated and untreated groups and don’t look at the long-term effects.
In theory, MSC treatments will be most effective if cells are injected into the injured area as soon as possible. However, most current treatments require several weeks to collect cells, grow them in a lab then inject the MSCs back into the injured horse. Researchers are considering other ways to more quickly obtain large numbers of MSCs for treatments.
Treatments using iPSCs have great potential for future treatments in humans and horses, but researchers are still determining how to reliably make specific cell types in uniform batches that can be used for treatments.
What stem cell treatments are currently being used in horses?
Musculoskeletal injuries are a significant and costly health problem in horses. Mesenchymal stem cells (MSCs) are one way such injuries are currently treated. As in humans, equine MSCs can be harvested from bone marrow and other tissues, and then grown in culture. However, since these are actually mixed cell populations containing only a minute fraction of true stem cells among many other specialized (non-stem) cells, a more appropriate name for these preparations is mesenchymal stromal cells.
These cells are most frequently harvested from the bone marrow by puncturing the sternum (breast bone) or ilium (pelvic bone). Alternatively, they are obtained from fat collected from under the skin by making a small wound on the animal’s rump. After collection, bone marrow samples are grown in culture for 2-3 weeks to increase the number of stem cells or they are concentrated by centrifugation and transplanted immediately back to the patient. Samples from fat are often not grown in culture but are transplanted back into the patient within a few hours of collection. Transplantation is performed by injection of cells into a tendon lesion, injection into a joint or injection into a local vein to achieve a wider distribution of cells throughout the area of disease.
Bone marrow cells were first used to treat tendon injuries in horses in the UK in the early 2000s. Since then, numerous studies have been carried out to understand the characteristics of equine MSCs and test their clinical applicability in horses. Clinical trials have tested MSCs from bone marrow, and to a lesser extent from other tissues such as fat or umbilical cord, to treat tendon injuries, osteoarthritis and other cartilage and ligament injuries. Some beneficial effects on the recovery of horses from injury have been observed, indicated by an earlier return to sporting activities or a lower incidence of re-injury in patients treated with MSCs.
What are the limitations of using MSCs to treat musculoskeletal injuries in horses?
Stronger evidence is still needed, from trials comparing large numbers of both treated and non-treated animals and carrying out appropriate follow-up to determine long-term effects of treatments.
The most effective way to administer stem cell treatments to horses still needs to be established too. We don’t yet know which is the best source of MSCs, how many cells should be transplanted, whether or not the cells should be differentiated in culture before being transplanted, and when and how often to administer treatments.
In spite of that, the use of stem cells in horses continues and for some of their current applications (for example, laminitis) there is no evidence that they actually work. At the moment equine therapies use autologous cells - cells that are collected from a patient and transplanted back into the same animal after processing. The number of stem cells that can be harvested from any one horse is very low. In fact, from some animals no stem cells at all are obtained.
The harvested cells can be grown in the laboratory to increase their numbers before being put back into a patient, but this delays the onset of treatment after injury or disease, often for 2-4 weeks. For this reason, allogeneic cells – cells taken from one animal and transplanted into another - may be beneficial. They could potentially be the basis for an off the shelf, ready to use treatment with proven efficacy. Research is now underway to find adequate and safe allogeneic sources of equine stem cells.
Pluripotent stem cells, unlike MSCs, can produce any cell type in the body. Harvesting the pluripotent stem cells that are naturally found in horse embryos has proven challenging, but using laboratory techniques developed for human cells, cells taken from horse skin have been reprogrammed to become pluripotent stem cells. These cells, called induced pluripotent stem cells (iPSCs), are similar to those naturally found in horse embryos and offer some advantages over other stem cells. They can be produced in vitro from any given patient and can be used to generate any type of cell in the body - for clinical transplantation or to study diseases in a petri dish.
The first equine iPS cells were made in 2011. Since then, researchers have been able to make equine nerve cells in the laboratory from iPS cells, and are working on methods to produce other cells that may one day be clinically useful – including, for example, MSCs.
Equine iPSCs could also be powerful tool to study normal body development in the lab, to understand how specific diseases develop in horses and to test new drugs to treat them.
Equine iPSCs have enormous potential, but several limitations will need to be overcome before they can be safely considered for therapy in horses. Most importantly, researchers need to learn how to safely control the differentiation of iPSCs into specific cell types of interest (rather than into multiple tissue types). The first clinical trials with human iPSCs are already underway (specifically, in the treatment of age-related macular degeneration) providing hope that these pluripotent cells may also be useful in developing new treatments for horses.
Lead image: "Tobiano" by Jean-Pol GRANDMONT, bearbeitet von Kersti (Licensed under CC BY 2.5 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Tobiano.jpg#/media/File:Tobiano.jpg
All other images copyright Xavier Donadeu, The Roslin Institute, University of Edinburgh