The development and regulatory approval of stem cells for human applications has largely outpaced that of veterinary medicine due to the unmet medical need for therapies that target underlying disease pathology, not just the clinical signs. Yet we are hearing a growing demand that pets receive and deserve a human standard of care. So, we are faced with a glimpse of what the future of animal health may look like as veterinary regenerative medicine catches up to its human counterpart.
Stem cells have emerged as a promising therapeutic category for veterinary medicine, with near-term clinical applications showing promise for various diseases. This is due to their potent immunomodulatory and anti-inflammatory functions and ability to aid in the natural healing of many tissues.
Because many of the common acute and chronic diseases that affect pets are caused by a dysregulated immune system or biological process, there is a significant clinical need and market opportunity to bring targeted therapies that can re-establish the normal biological function of tissues and organs to pets. Stem cells are a disease-modifying therapy that, when administered intravenously, target sites of disease and immune dysregulation in the body and naturally restore the body to its normal state without disrupting peripheral organ function.
Stem cells are a disease-modifying therapy that […] target sites of disease and immune dysregulation in the body and naturally restore the body to its normal state without disrupting peripheral organ function
Currently, there are only a few allogeneic stem therapies with marketing authorisation in Europe, and these address osteoarthritis in dogs and horses and ligament injuries in horses. The anticipated conditional FDA approval of an allogeneic stem cell therapy for cats with refractory feline chronic gingivostomatitis (FCGS) contributes to a notable shift towards stem cell therapy becoming a mainstream standard of care.
Here, we discuss the scientific innovation supporting allogeneic stem cell therapy to address refractory FCGS and its broader clinical impact.
What is feline chronic gingivostomatitis?
FCGS is a severe immune-mediated inflammatory condition characterised by painful mucosal lesions affecting the oral cavity, including the gums and back of the mouth. Symptoms of the disease include varying degrees of oral pain and discomfort, a loss of appetite, decreased grooming behaviour, weight loss, excessive salivation (ptyalism) and an overall decline in the cat’s quality of life.
The cause of FCGS is still not fully understood, but it is scientifically accepted that it results from the host’s immune system reacting to prolonged oral exposure to antigens, which leads to significant inflammation and high levels of effector T-cells (Vapniarsky et al., 2020).
Unfortunately, there is no cure for FCGS, and current medical management involves extensive tooth extraction and lifelong treatment with medications, such as corticosteroids, non-steroidal anti-inflammatories, analgesics and antibiotics, to control the inflammation, pain and recurrent oral infections.
The incredibly high burden of care for the veterinarian, owner and patient is further complicated when we take into account the discouraging statistic that as many as 50 percent of cats are refractory to medical management and go on to suffer, be euthanised or die from the decline in quality of life due to the disease (Trone, 2023).
Allogeneic stem cell therapy for FCGS
Building on the growing momentum and the body of research supporting the use of stem cells to treat diseases in pets, allogeneic stem cell therapy to treat cats with refractory FCGS is being developed. In fact, it is on track for conditional FDA approval, moving this treatment even closer to the clinic. This investigational stem cell therapy is the only known therapeutic option shown to be effective for refractory FCGS in pilot studies. It has been shown to help improve painful oral lesions, increase the affected cat’s quality of life and prolong the lifespan of these beloved family members.
Uniquely distinct from autologous approaches that use stem cells from individual patients, this allogeneic therapy uses mesenchymal stem cells (MSCs) sourced from the uterus (UMSCs) of FDA-qualified, specific pathogen-free donors – tissue that is normally discarded during a routine spay. These can be optimised and scaled to reliably provide more treatments to more patients and to do so faster and with the confidence of established efficacy, safety, sterility, potency, purity and stability.
In addition to the stem cells’ innate ability to interact with cells of the immune system to restore balance, these cells interact with tissues and naturally restore function […] offer[ing] hope for therapeutics that can modify disease onset, progression and repair
The immune-mediated nature of FCGS makes UMSCs a compelling first-choice treatment. MSCs regulate immune responses by secreting factors that directly reduce inflammation and alter T-cell and B-cell numbers, proliferation and function. This characteristic suggests that MSCs could be well suited for addressing several immune-mediated inflammatory diseases, not just FCGS. In addition to the stem cells’ innate ability to interact with cells of the immune system to restore balance, these cells interact with tissues and naturally restore function. This has been demonstrated for cartilage and tendons and offers hope for therapeutics that can modify disease onset, progression and repair (Depuydt et al., 2022; Spaas et al., 2015).
What does the research say?
Early clinical studies have shown that UMSCs are highly effective for FCGS with an emphasis on quality of life and owner assessment (Taechangam et al., 2023).
In two pilot studies investigating UMSCs for cats with refractory FCGS, owners’ assessments of improvement following UMSC therapy in the two studies were 78 and 83 percent at day 90, respectively. Two injections effectively reduced oral lesions in the cats by 43 percent and 48 percent, respectively. This builds on a previous independent study in which more than 50 percent of cats that would have been euthanised due to FCGS continued to thrive with their owners following treatment with stem cells (Soltero-Rivera et al., 2023).
In addition to the previous research, several other clinical studies have produced strong data demonstrating the clinical efficacy of MSCs as a promising therapeutic option for FCGS and other immune-mediated inflammatory diseases (Arzi et al., 2017; Soltero-Rivera et al., 2023).
Mesenchymal stem cells: a compelling treatment?
The disease-modifying capabilities of MSCs hold significant clinical potential beyond just FCGS. Conventional immunosuppressant drug therapies such as corticosteroids, cyclosporine or monoclonal antibodies (mABs) are characterised by numerous off-target effects that can limit long-term use and effectiveness, thus necessitating the development of new therapeutics that are effective and safe, and that target the global dysregulation and disease pathology. In the case of FCGS, cats refractory to medical management (including extraction of all their teeth) currently have no hope until stem cell therapy becomes a reality.
Aside from FCGS, MSCs will likely become an important therapeutic approach to address other companion animal diseases, including atopic dermatitis, irritable bowel syndrome, feline asthma, osteoarthritis, chronic kidney disease, keratoconjunctivitis sicca and many others.
Final thoughts
Current veterinary treatments only address the clinical signs or symptoms of diseases, such as controlling fever, reducing nausea, reducing pain or controlling infection. These treatments do not alter the root cause – the dysregulated or pathological biological processes – of the underlying disease. For some diseases, such as refractory FCGS, there are no effective or safe therapeutics available.
Currently, stem cells are the leading disease-modifying treatment in development that address the underlying drivers of disease rather than just the symptoms
Currently, stem cells are the leading disease-modifying treatment in development that address the underlying drivers of disease rather than just the symptoms. The development of an allogeneic stem cell therapy for refractory FCGS has laid the foundation for UMSCs as an emerging new class of FDA-approved therapeutics for treating a plethora of disease conditions in veterinary medicine.
We are witnessing the use of stem cells to transform medicine both in humans and in pets. This “off-the-shelf” stem cell therapy will likely represent the first of many in what will be the next generation of veterinary medicines, where we can treat the root cause of disease rather than just the symptoms to significantly improve the lives of pets and their families.
