Abstract The recommended treatment for feline chronic gingivostomatitis (FCGS) is tooth extraction to reduce pain and inflammation. The use of intravenous feline adipose tissue derived MSC (fAT MSC) as immunomodulators has been reported in refractory cases with favorable outcomes. However, intravenous administration may be associated with adverse events and pulmonary cell trapping. This study assessed the clinical and histologic effects of fAT MSC administered intramucosally in cats with FCGS undergoing tooth extraction. For this purpose, two groups were studied: (1) control, treated with premolar and molar extraction (PME) (n=10), and (2) treated with PME plus a single intramucosal dose of 10 million fAT MSC at the time of surgery (n=10). Cats were tested for FIV antibodies and FeLV antigen. Monthly clinical follow up was performed using the Stomatitis Disease Activity Index (SDAI) scoring system, together with hematological and biochemical analyses. Caudal oral mucosa biopsies were collected at days 0 and 30 for histopathological evaluation of the inflammatory infiltrate by classification using the scoring system for severity of microscopical inflammatory change. The study population had a mean age of 7.5 years, with 67% males and 33% females; 20% tested positive for FIV and 25% for FeLV. Lifestyle distribution was mixed in 62%, indoor in 24%, and outdoor in 14%, with 95% cohabiting with other cats. Among the 20 cats included in the study, a decrease in SDAI scores was observed at day 15, 30, 90, 120 and 180. At day 30, 75% of the cats demonstrated clinical improvement, and when analyzed by group, improvement was observed in 60% of the treated cats and 89% of the controls. Treated group had a mean SDAI of 15.1±6.8 at day 0 and 9.2±3.3 at day 30 (p=0.001), while the control group scored 13.5±3.7 at day 0 and 6.9±3.0 at day 30 (p=0.01). Interestingly, by day 90 the overall rate of improvement reached 83%, with 90% in the treated group and 75% in the control group. The most frequent hematological alterations were anemia, eosinophilia, lymphopenia, and monocytosis, while biochemical changes included hyperglobulinemia, increased total protein, and hypoalbuminemia. Hematocrit and hemoglobin increased significantly at days 15 and 60 post treatment (p=0.0003 and p=0.003, respectively) in treated cats compared with controls. Oral mucosa biopsies stained with H&E were analyzed in 9 cats (4 controls and 5 treated) at days 0 and 30.

A decrease in inflammation and a correlation between histological score and SDAI were observed. At day 0, the median inflammatory severity score was 3 in both groups while at day 30, the treated group scored 2 versus 1.5 in controls. In conclusion, both treated and control groups showed clinical improvement in most cases, accompanied by a reduction in inflammatory infiltrates in the caudal oral mucosa. Notably, the treated group exhibited an increase in hematocrit and hemoglobin values compared with controls. No adverse reactions were observed during o after intramucosal administration of fAT MSCs. These findings suggest potential systemic effects of intramucosal administration of fAT MSCs in combination with PME, supporting further research with larger cohorts.