Cell therapy is widely recognized for its transformative potential in human medicine, particularly in regenerative medicine and oncology. However, the field has also made significant strides in veterinary medicine, where therapies — especially those utilizing mesenchymal stem cells (MSCs) — have been deployed with greater regulatory flexibility. Veterinary applications provide an opportunity to explore real-world efficacy, particularly in treating orthopedic injuries in horses and dogs. These advancements not only benefit animal health but also offer translational insights that could accelerate progress in human clinical trials.
The following article is adapted from Nice Insight’s Cell Therapy: Market Insight, CDMO Pricing and Competitor Benchmarking report and explores the evolving landscape of veterinary cell therapies. It examines their scientific foundation, regulatory considerations, commercial availability, and potential to inform human medical advancements through the One Health Initiative.
In 1991, Dr. Arnold Caplan described the role of mesenchymal stem cells (MSCs) in embryonic bone and cartilage formation, and in tissue regeneration and repair in adults. He further hypothesized that these cells could be used therapeutically as a form of regenerative medicine.1 The lack of effective treatment alternatives, combined with a tolerant regulatory framework, resulted in a rapid transition from research to veterinary clinical practice. In 2001, Douglas Herthel published a retrospective study of 100 horses he had treated with intralesional injections of autologous bone marrow over the preceding six years. Of those 100 horses, 84 returned to full work and soundness after 6 months.2 Shortly afterwards, researchers at the Royal Veterinary College in London published a case study outlining the isolation, characterization, expansion, and reimplantation of autologous MSCs into an 11-year-old polo pony with superficial digital flexor tendon (SDFT) damage.3
MSCs are multipotent adult stem cells that can both self-renew and differentiate into specialist cell types including bone, cartilage, ligaments, tendons, fat, skin, muscle, and connective tissue.1 Proliferation and differentiation are activated through cell signaling, and MSC behavior and function are influenced by interactions with other stem cells, neighboring differentiated cells, adhesion molecules, the extracellular matrix, growth factors, cytokines, and other components of the stem cell “niche.”4,5 Initial research postulated that the therapeutic potential of MSCs was a direct result of differentiation into new tissue cells. However, more recent studies indicate that the regenerative power of MSCs in fact stems from their ability to influence the immune system, sense tissue damage, and migrate to the source and promote tissue repair.6,7
MSCs are found in all adult tissues, are relatively easy to isolate, yield a high number of cells upon harvesting, and have no ethical barriers to use, making them especially promising for stem cell therapies. In veterinary medicine, preferred tissue sources for MSCs are adipose tissue and bone marrow, both of which yield high numbers of stem cells. In addition, MSC isolation from adipose tissue is minimally invasive.6
Since its initial application in horses, veterinary stem cell therapy has since expanded to companion animals, predominantly dogs and cats. In dogs, for example, several studies have reported beneficial effects of MSC therapies to treat cranial cruciate ligament injuries.8–10
Following early successes with stem cell therapies in orthopedic conditions in horses and dogs, MSC therapies have been further investigated in numerous other veterinary diseases. However, despite positive findings in several indications — including severe refractory gingivostomatitis in cats,11 inflammatory bowel disease in dogs,12 enteropathy in cats,13 degenerative hepatopathy in dogs,14 and wound healing and eye disease in horses (reviewed in Voga et al. 20206) — the study sizes have been too small, the protocols insufficiently optimized, and the research insufficiently systematic to make a definitive conclusion as to the efficacy of stem cell therapies in any of these indications.
Veterinary Applications for Cell Therapies
The human cell therapy landscape for both approved and pipeline therapeutics is dominated by oncology treatments.15 In veterinary medicine, however, the development of cell therapies has been driven primarily by the desire to achieve full functional restoration following orthopedic injuries.
Horses and dogs are both prone to tendon, ligament, and joint injuries, which have similar characteristics to those experienced by humans. Similar to human athletes, competitive horses, such as racehorses, event horses, show jumpers or polo ponies, are at particularly high risk of sports-related stress or repetitive strain injuries. Competitive horses frequently experience equine SDFT strains, and distal deep digital flexor tendon (DDFT) injuries are common in elite showjumping.16
As tendon and ligament injuries heal, the formation of scar tissue, which is functionally deficient compared with healthy tissue, leads to reduced flexibility and increased risk of reinjury. These types of injuries are traditionally treated by cooling, bandaging, and a period of rehabilitation exercises. They can also be treated with systemic or local corticosteroid or anti-inflammatory drugs, but often require surgical intervention. However, none of these measures allow for complete tissue healing.6 Orthopedic problems are the cause of 70% of days-lost to training in showjumpers and racehorses, and in many cases, the horse will never return to its preinjury performance.17,18 In fact, osteoarthritis is the leading career-ending condition and cause of chronic lameness in horses.19
Veterinary Stem Cell Therapies are Commercially Available Without Regulatory Approval
Perhaps unsurprisingly, particularly in the United STates, commercial interest in veterinary applications of stem cell therapies rapidly outpaced regulatory control. While the first companies supplying allogeneic MSCs or services to support the isolation and expansion of autologous MSCs were established in the early 2000s, the FDA guidance for developing cell-based products for animal use wasn’t published until 2015.20
To date, no cell therapy products for veterinary medicine have been approved by the FDA, which is likely because published peer-reviewed studies demonstrating conclusive benefits are still lacking for many diseases, despite a growing body of data suggesting that stem cell therapies are effective, particularly for orthopedic injury. The American Veterinary Medical Association takes a similarly conservative policy position.21 Despite muted regulatory enthusiasm, stem cell therapies are reasonably accessible for both horses and pets for osteoarthritis and some tendon and cartilage joint injuries. MSC therapies for dogs cost somewhere in the range of $2,000–$3,000, but this is now covered under some pet insurance policies.22
In Europe, the European Medicines Agency (EMA) has approved two MSC products for commercial use. Arti-Cell® Forte is given as a single injection into an affected joint for the treatment of mild to moderate lameness resulting from joint inflammation in horses, while HorStem® is approved for the treatment of mild to moderate osteoarthritis in horses.23 In the UK, veterinary medicines are regulated by the Veterinary Medicines Directorate, and specialist centers such as the Royal Veterinary College are approved to carry out stem cell therapies in horses and dogs for certain indications or to supply cell products to veterinarians.24
Potential for Veterinary Research to Inform Human Trials
Under the One Health Initiative, which is defined by the World Health Organization (WHO) as an integrated, unifying approach to balance and optimize the health of people, animals, and the environment, some veterinarians suggest that the body of data supporting the use of MSCs for orthopedic indications in animals can and should be considered in the assessment of novel human therapies. In particular, they argue that lack of fidelity in traditional animal models leads to later clinical failures, and that therefore treatment of naturally occurring diseases in companion animals might prove a better indication of human clinical success. In this argument, companion animal models are more similar to human models due to the fact that, like humans, their naturally occurring diseases are a result of complex interactions between multiple genes and environmental factors, while their longer life span and larger size allows for more directly translatable diagnostic and treatment procedures.11
On the other hand, there is no central, searchable database for veterinary clinical trials, and, as discussed above, veterinary clinical trials are often small, sporadic and not completed in a systematic phased manner, as human trials are. Therefore, while it may be possible to amass sufficient data to support a general suggestion of efficacy in certain indications, it is harder to argue that there would routinely be sufficient veterinary trial data available to directly inform in-human clinical studies. Nevertheless, based on its experience delivering veterinary stem cell therapies, cell therapy company VetStem has spun out a sister company, Personalized Stem Cells, to conduct human clinical trials so that you can also be “treated like a dog.”25 They received FDA approval of their investigational new drug (IND) to launch a clinical trial for use of autologous MSCs to treat osteoarthritis in 2019.26
Veterinary Research iPSC and CAR-T Cell Therapy
Understanding of veterinary species-specific iPSCs and their corresponding regulators of pluripotency lags behind that of human iPSCs, which has delayed their evaluation in veterinary clinical trials.11 To date, one pilot study has aimed to optimize the generation of neural progenitor cells (NPCs) from canine iPSCs and test their safety in dogs with spinal cord injuries. This study found that, although NPCs derived from canine iPSC could differentiate into mature neural cells, neither of the two dogs that were injected with canine NPCs experienced any meaningful improvement in their condition.27
Veterinary research into CAR-T cell therapies is still in its infancy. A first-in-species trial investigated the use of CAR-T cell therapies in dogs with spontaneous diffuse large B cell lymphoma (DLBCL). However, this trial injected only low numbers of CAR-T cells into each dog, and the study objective was primarily to determine whether dogs might provide a more faithful representation of the clinical challenges experienced by humans during CAR-T cell therapy trials than rodents, and to establish their feasibility as a model for addressing manufacturing issues.28
More recently, the Gates Institute in Colorado has launched a clinical trial of CAR-T cell therapies in dogs with osteosarcoma, with the hope that this research might inform future human clinical trials into use of CAR-Ts for solid tumors.29 Current CAR-T cell manufacturing platforms are likely to prove cost prohibitive for veterinary use, so if these cell therapies are to progress beyond improved preclinical models to inform human trials, it will be essential to establish alternative reagents, manufacturing processes, and product profiles that can deliver CAR-based therapeutics to animal patients at a significantly lower cost.30
References
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