Mesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n = 3) or substantial clinical improvement (n = 2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6–24 months). In this study, cats with 15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype. Significance: This study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats. The findings demonstrate that this therapy resulted in complete clinical and histological resolution or reduction in clinical disease severity and immune modulation in most cats. This study also identified a potentially useful biomarker that could dictate patient enrollment and shed light on immune modulation mechanism. As a naturally occurring animal model, FCGS also provides a strategic platform for potentially translatable therapy for the treatment of human oral inflammatory disease.

Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti-fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8^lo cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710–1722

Objective—To describe CT findings in dogs and cats with temporomandibular joint (TMJ) disorders. Design—Retrospective case series. Animals—41 dogs and 17 cats. Procedures—Medical records and CT images of the skull were reviewed for dogs and cats that were examined at a dentistry and oral surgery specialty practice between 2006 and 2011. Results—Of 142 dogs and 42 cats evaluated, 41 dogs and 17 cats had CT findings consistent with a TMJ disorder. In dogs, the most common TMJ disorder was osteoarthritis; however, in most cases, there were other TMJ disorders present in addition to osteoarthritis. Osteoarthritis was more frequently identified at the medial aspect rather than the lateral aspect of the TMJ, whereas the frequency of osteoarthritic involvement of the dorsal and ventral compartments did not differ significantly. In cats, fractures were the most common TMJ disorder, followed by osteoarthritis. Clinical signs were observed in all dogs and cats with TMJ fractures, dysplasia, ankylosis, luxation, and tumors; however, only 4 of 15 dogs and 2 of 4 cats with osteoarthritis alone had clinical signs. Conclusions and Clinical Relevance—Results indicated that TMJ disorders were frequently present in combination. Osteoarthritis was the most common TMJ disorder in dogs and the second most common TMJ disorder in cats. Computed tomography should be considered as a tool for the diagnosis of TMJ disorders in dogs and cats with suspected orofacial disorders and signs of pain. (J Am Vet Med Assoc 2013;242:69–75)

Feline chronic gingivostomatitis (FCGS) is a disease characterized by protracted and potentially debilitating oral inflammation in cats, the etiology of which is currently unknown. The purpose of this review is to apply an evidence-based medicine approach to systematically review and critically evaluate the scientific literature reporting the outcome of medical and surgical management of FCGS. Those articles meeting inclusion criteria were reviewed and assigned an “Experimental Design Grade” (EDG) and an “Evidence Grade” (EG) in order to score relative strength of study design and produced data. Studies were evaluated and compared, especially highlighting the treatments, the outcomes, and the therapeutic success rates. This review found a lack of consistency between articles’ data, rendering direct comparison of results unreliable. The field of FCGS research, and ultimately patient care, would benefit from standardizing studies by adopting use of a consistent semi-quantitative scoring system and extending follow-up duration. Future researcher should commit to large prospective studies that compare existing treatments and demonstrate the promise of new treatments.