Two Reviews of Stem Cells for Horses

From Texas A&M University and the Virginia-Maryland Colleges of Veterinary Medicine come two reviews of the use of mesenchymal stem cells for horses with musculoskeletal injury, as well as other inflammatory conditions.

Not to be confused with plasma products that may be helpful to treat some injuries but aren’t living stem cells, the term “stem cells” includes a range of living cell preparations harvested from a species for use in that same species. They are harvested from a donor and given to a recipient, which may be the same individual or a second (ideally tissue-matched) individual. They can be harvested from fat tissue, bone marrow, or umbilical cord blood.

In addition to being able to enhance the immune system, they are anti-inflammatory; and most impressively, they can differentiate into different types of tissue to replace, repair, or rescue damaged cells. They can be fresh or frozen, used as collected or grown first in culture, used as is, or activated to trigger certain functions. All these variables make it difficult to identify treatment protocols that are effective for different types of injury or illness, but they also create the possibility of novel treatments for many conditions.

The paper by Watts, referenced here, discusses the use of stem cells for musculoskeletal injury. They report good evidence for stem cell use in treating tendon and ligament injuries, particularly when used before the accumulation of fibrous scar tissue. Rather than forming scar tissue, stem cells may differentiate into the type of healthy cells that are injured (tendon, ligament, cartilage) so injured cells are replaced with more functional tissue. They can also modulate the inflammatory response so these tissues heal faster, or both.

One of the first clinical uses for stem cells in horses was for the treatment of bowed superficial digital flexor (SDF) tendons. Long-term follow-up of jump-race horses treated with stem cells for bowed tendons demonstrated a reinjury rate of only 25%, substantially better than that reported for other treatments.

In controlled studies of SDF tendon healing, those treated with stem cells had lower structural stiffness and more normal cellular and histochemical characteristics. Clinically, 77% of warmbloods with tendon and ligament injuries returned to full work, and racehorses with injured SDF tendons were significantly more likely to return to racing compared with untreated controls. For cartilage injury, intraarticular corticosteroid injections may have a more profound immediate effect, but stem cell injections could have more long-term beneficial effects when this therapeutic approach is better developed.

The use of stem cells for the treatment of other inflammatory conditions of the horse was reviewed by Barrett. Their discussion emphasized the importance of stem cell signaling by way of the chemicals, enzymes and bioactive molecules they release or stimulate. Stem cells can even donate intracellular organs (mitochondria) to ailing cells such as cartilage cells to rescue or repair them. Unfortunately, while effective in mice, stem cells haven’t been shown to help combat endotoxemia in the horse, but the authors point out this simply could be because the right combination of cell type, preparation and dose might not have been tried.

Similarly, their use for equine asthma and gastrointestinal diseases such as gastric ulcers and colitis offers some promise if successfully extrapolated from mouse models. Stem cells also have been shown to improve hoof growth and vascular perfusion in controlled studies of horses with laminitis. However, more work is needed to identify the best approaches before they are ready for broad clinical use on foundered horses.

In addition to the many variations of how stem cells are collected, handled, cultured and/or pretreated to stimulate different types of cellular activity, the authors point out that retreatment of a horse using stem cells collected from another horse donor can be problematic because the first treatment can prime an immune response that kills the cells of a second treatment. This stem cell rejection might not harm the horses, but as stated by Watts, dead stem cells are not functional stem cells; so living stem cells are essential for the treatments to succeed.

— Watts AE. Vet Clin Equine 2023 DOI:10.1016/ j.cveq.2023.07.003 and Barrett JG et al. Vet Clin Equine 2023 DOI:10.1016/j.cveq.2023.07.004

Stem Cells for Racehorses with Suspensory Desmitis

Veterinarians from the Rood and Riddle Equine Hospital in Kentucky used 9 years of medical records to examine the performance of Thoroughbred racehorses following stem-cell treatment for suspensory ligament branch injury. They looked at the ability to race, as well as factors that might influence the prognosis for a successful return to racing.

Sixty-nine horses presented with lameness and confirmed lesions in a branch of the suspensory ligament that were amenable to treatment. At the time of diagnosis, the lesions were injected with stem cells derived from umbilical cord blood. At this same time, bone marrow also was harvested from the injured horse.

These stem cells were isolated and grown or multiplied over 2-3 weeks and then injected into the same horse when ready and again 6, 10 and sometimes 14 weeks after the second treatment.

Most (71%) of the treated horses raced following treatment, and those that had raced before injury and males were more likely to do so. For those that raced before and following injury, earnings and earnings per start were not significantly different following treatment. On average these horses continued racing for 29.5 months. Although no comparisons can be made to horses treated in other ways, with the high rate of returning to racing the authors suggest stem cells are a viable option for treating suspensory ligament injuries.  

— Hansen SH et al. EVJ 2023 DOI:10.1111/evj.13980