August 2, 2016
Although still in its infancy, the field of regenerative medicine is maturing and growing. The thought of harvesting adipose tissue or bone marrow is not as daunting a task as it once seemed, and several commercial kits make processing those tissues in-house easy. As such, we are now better able to treat injuries that were once thought to have a poor prognosis, poor long-term outcome, and reliant on supportive therapies only (e.g., anti-inflammatory drugs, rest, repeat). Based on the recently published studies and the round table discussion on regenerative therapies at the 2015 Annual Convention of the American Association of Equine Practitioners, here are 3 easy ways to incorporate stem cell therapy into any equine practice to maximize healing and return to performance while minimizing re-injury.
Injuries of the superficial digital flexor tendon (SDFT) were among the inaugural targets of stem cell therapy, and probably remain one of the most commonly treated structures. Therefore, they provide the bulk of the data available on stem cell therapy in horses.
In one study published in 2013, horses with naturally occurring tendinopathy of the SDFT were treated with 10 x 106 mesenchymal, bone marrow-derived (BM-MSC), culture-expanded stem cells injected intralesionally. After treatment, horses were box-rested with the limb bandaged for 7 days. They subsequently underwent a standardized exercise rehabilitation regimen of walking for 3 months then a walk/trot combination for the second 3 months of the study. The hypothesis was that stem cell therapy would induce the production of a tendon matrix that more closely resembles normal tendon rather than the weak, fibrous scar tissue formed by natural repair.
Key findings were that treated tendons exhibited statistically significant improvements in terms of biochemical, morphological, and compositional parameters than control tendons and that no adverse events were noted in any treated horse.
Other studies support these data; however, the fate of stem cells injected intralesionally remains unclear. According to a 2010 study co-authored by stem cell guru Roger Smith, VetMB, PhD, DEO, Dipl. ECVS, MRCVS, a professor of equine orthopedics at the Royal Veterinary College in the United Kingdom, MSC survival is less than ideal. Further, data presented at the 2011 North American Veterinary Regenerative Medicine Association Conference suggest that not all stem cells stay where they are put.
At the 2015 AAEP, Rich Redding, DVM, MS, Dipl. ACVS, clinical professor of equine surgery at North Carolina State College of Veterinary Medicine, and Ashlee Watts, DVM, PhD, Dipl. ACVS, of Texas A&M College of Veterinary Medicine’s Department of Veterinary Medicine & Biomedical Sciences, suggested that perhaps stem cells don’t need to remain viable long-term following injection. Instead, they may only need to remain viable long enough to create an environment that allows resident cells to do a better job repairing the injury themselves. While the specific fate of stem cells once delivered remains elusive, the benefits of intralesional stem cell therapy appear obvious to many.
The “gold standard” of stem cell therapy (if we actually have enough data to suggest there is a gold standard at this point) seems to be cultured BM-MSCs. This technique isolates the actual MSCs from “other” cell types, allowing their expansion, and the delivery of millions of cells at one time — a feat that cannot be achieved using an in-house kit. The major drawback is time. Culturing takes several weeks, leaving an injured horse reliant on supportive care and subject to scarring.
A viable alternative is sending part of the bone marrow aspirate to a certified laboratory for culturing and using the remainder of the sample in-house and treating the horse immediately. This approach allows at least some stem cells to do whatever job we think they do while we wait for the gold (see above regarding the lack of data on the fate of stem cells post-administration).
Some practitioners are also using stem cell therapy in conjunction with platelet-rich plasma (PRP). The idea is that the PRP clots following injection and therefore forms a type of scaffold for the stem cells to perch on. Again, whether the stem cells need to remain intralesionally remains debatable, but the theory is reasonable based on our current knowledge base.
Intralesional injection of soft tissues and even joints isn’t the only option. In small animals, IV administration of stem cells via the jugular vein is a common approach for treating diffuse lesions or “hard to reach” places. In equine medicine, what better indication to try administering stem cells via regional perfusion than to treat horses with laminitis? Several attendees at the 2015 AAEP Regenerative Medicine round table discussion reported using both arterial and venous regional perfusion in addition to coronary band injections. Unlike small animals, IV injections via the jugular vein are unlikely to be a reasonable option for horses due to the large dose likely required.
Horses and humans share many similarities in terms of health and disease. Insulin resistance/metabolic syndrome, asthma, and musculoskeletal conditions such as tendinopathy and joint disease/osteoarthritis (OA) immediately spring to mind. While equine medicine frequently benefits from advances in human medicine, veterinary research in regenerative medicine is paving the way for humans. Equine practitioners are encouraged to experiment and try different techniques on different types of lesions and, most importantly, share your findings.
“The only way we are going to make any clinical advancement using regenerative therapies in the field to keep horses sound is with careful science and reporting so we can figure out what works and what doesn’t,” Watts advised during the 2015 AAEP roundtable discussion.
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