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Efficacy of stem cell therapy for chronic gingivostomatitis in cats

Arzi B, Clark K, et al. Therapeutic efficacy of fresh, allogeneic mesenchymal stem cells for severe refractory feline chronic gingivostomatitis. Stem Cells Trans Med. 2017 Jun 15. doi: 10.1002/sctm.17-0035. [Epub ahead of print] (Winn funded study)

An exciting area of research currently is stem cell-based therapy. This is due in large part, beyond the capability to regenerate damaged tissues, to mesenchymal stem cells (MSCs) having unique immunomodulary characteristics and therefore can improve outcomes of diseases that result in abnormal immune responses. Therefore, MSCs are a promising therapy in cases of immune-mediated inflammatory disease.

The authors previously demonstrated that this therapy by using allogeneic adipose-derived stem cells result in delayed clinical and histologic resolution and immune modulation for cats with severe refractory feline chronic gingivostomatitis (FCGS). Along with efficacy, they demonstrated the safety of MSCs to treat this syndrome in cats.

FCGS is a very painful and debilitating severe oral mucosal inflammatory disease. As a disease syndrome of cats, it is estimated to affect 0.7% to 12% of the general cat population. The primary clinical signs are moderate to severe mouth pain and discomfort, loss of appetite, decreased grooming, weight loss and significant drooling. Many cats are on long-term immunosuppressive therapy with the potential for associated risks and side effects from treatment. Full or near-full mouth tooth extraction is considered the current standard of care for the condition. 70% of cats respond to tooth extractions, the remaining 30% do not respond. A number of the severely affected cats that do not respond to treatment are often euthanized because the condition is so debilitating.

While autologous (self) adipose stem cells (ASCs) are nonimmunogenic and safe for use in cats, drawbacks include isolation time and lack of proliferation of sufficient cell numbers for treatment.  Allogeneic (a different cat) ASCs have the advantage of being more available, higher quality control, decreased cost and fewer anesthetic events for recipients. Intravenous injection of allogeneic ASCs appears safe with no significant adverse events reported.

This study evaluated using fresh allogeneic ASCs for treatment of FCGS in seven cats. Each cat received two intravenous injections of ASCs one month apart.  Four of the seven cats responded to treatment with complete clinical remission or substantial clinical remission. Three cats did not respond to the therapy. The IV treatment was well tolerated and considered safe for cats with severe FCGS.

In this current study, the authors noted the pretreatment percentages of blood CD8+ T cells and the resultant CD4/CD8 T cell ratio mirrored the findings in the prior autologous stem cell study. Yet, this time at the 6 months post allogeneic ASC therapy, these immune subsets did not notably change regardless of the cat’s clinical outcome. In addition in this study, two pro-inflammatory serum cytokines did not show any consistent change after administration.

The authors state they discovered two potential biomarkers of a successful response to autologous ASC therapy in cats with FCGS: a decreased pretreatment percentage of CD8lo cells which increase with cure, and increased serum IL6 after ASC infusion. They hypothesize these changes may be responsible for the generation of T regulatory cells and “reprogramming” of the immune response. This results in the long-term cure of these cats. They state the results also suggest that the potency and mechanism(s) of action differ for autologous and allogeneic ASCs in this type of oral inflammation. (VT)

See also:
Arzi B, Mills-Ko E, Verstaete FJ, et al. Therapeutic efficacy of fresh, autologous mesenchymal stem cells for severe refractory gingivostomatitis in cats. Stem Cells Transl Med. 2016 Jan; 5(1):75-86.