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Objective: This study aimed to characterize the clinical and histopathologic features of oral eosinophilic lesions in cats., Animals: 38 client-owned cats., Methods: The medical records database was searched for cats diagnosed with histologically confirmed eosinophilic oral lesions from 1997 to 2022. Information such as medical history, lifestyle factors, clinical presentation, and radiographic and histopathologic features was included for 38 client-owned cats. Response to treatment and long-term follow-up was also recorded., Results: The most affected site was the tongue, with approximately half of the affected cats showing signs of oral discomfort and difficulty eating or breathing. Ulcerative lesions were common, with two-thirds of patients showing more than 1 site affected. Histological samples had a classic appearance, whereas some had an atypical appearance characterized by degenerate collagen clusters associated with multinucleated giant cells. A significant association between lesion location, clinical signs, and prognosis was also found, with patients with palatal lesions being more likely to show respiratory signs and less likely to respond to treatment. Finally, treatment response was observed in most cases within 2 months of commencing therapy combining antimicrobial, and immunosuppressive treatment., Clinical Relevance: The results of this study demonstrate the importance of early diagnosis and treatment of cases of oral eosinophilic lesions in cats. Additionally, it emphasizes the need for a multimodal approach to treatment which should include antibacterial therapy. Of no less importance is that other systems may be affected in these patients, warranting a multidisciplinary approach to their management.

Practical Relevance: Feline chronic gingivostomatitis (FCGS) is a debilitating disease for cats and a challenge for veterinarians and cat caregivers alike. Recent literature indicates that the disease is immune-mediated in nature and likely associated with a chronic viral infection in patients with higher alpha diversity of their subgingival microbiome. The immune-mediated nature of FCGS includes both local as well as systemic effects, and the transcriptomic analysis of affected patients supports these findings., Treatment Options: Localized therapy in the form of surgical extraction of all, or nearly all, teeth continues to be the mainstay of treatment. For cats that do not respond to surgical management, medical management, in the form of immunosuppressive or immunomodulatory therapy, remains an option. Analgesia is of fundamental importance. Immunomodulation utilizing mesenchymal stromal cell therapy provides an alternative treatment avenue for refractory patients and likely targets the chronic viral infection present in this disease. The potential for treatment stratification and use of novel systemic treatment options may be revealed as the molecular pathways involved in this disease are better described., Aims: This review outlines current and emerging concepts linking available science pertaining to FCGS and clinical management of the disease., Evidence Base: The article draws on the best evidence base at this juncture and is also driven by the authors' collective experience of working on the disease for over a decade.

Feline chronic gingivostomatitis (FCGS) is a painful, immune-mediated, oral mucosal inflammatory disease in cats. The etiology of FCGS remains unclear, with evidence pointing potentially toward a viral cause. Full-mouth tooth extraction is the current standard of care, and cats that are non-responsive to extraction therapy may need lifelong medical management and, in some cases, euthanasia. Adipose-derived mesenchymal stromal cells (adMSCs) have been demonstrated to have advantages in the treatment and potentially the cure of non-responsive FCGS in cats. Therefore, adMSCs have attracted a series of ongoing clinical trials in the past decade. AdMSC therapy immediately after full-mouth tooth extraction was not explored, and we postulate that it may benefit the overall success rate of FCGS therapy. Here, we aim to summarize the current knowledge and impact of adMSCs for the therapeutic management of FCGS and to suggest a novel modified approach to further increase the efficacy of FCGS treatment in cats.

Management of temporomandibular joint (TMJ) fractures is challenging and is a subject of ongoing discussions and controversies in both the veterinary and human medical fields. Regardless of the management strategy, obtaining precise diagnostic imaging in the form of conventional or cone-beam computed tomography and potentially magnetic resonance imaging is pivotal for medical and surgical decision-making and prognostic purposes. The main objective of TMJ fracture management is a rapid return to normal function via restoration of pretrauma occlusion, range of motion, and masticatory function. With that in mind, it is prudent to distinguish between surgical interventions, such as condylectomy and open reduction with internal fixation, or to elect a conservative management approach. Given the diversity in TMJ fracture and patient circumstances, such as age, concomitant trauma, financial situation, and availability of expertise, the formulation of an individualized treatment plan is recommended. Knowledge of potential short- and long-term complications such as infection, malocclusion, ankylosis, fibrosis, and osteoarthritis is essential during TMJ fracture management. Importantly, as our clinical and research knowledge on managing TMJ fractures in dogs and cats grows, we rely on comparative evidence-based overviews, and inspirations from human medical experts to advance the veterinary field. Hence, this review discusses contemporary approaches to managing TMJ fractures and the outcomes in dogs and cats from a one-health perspective.

Objectives: This study aimed to characterize the clinical, radiographic and histopathologic features of early-onset gingivitis (EOG) and periodontitis in cats., Methods: The medical records database was searched for cats diagnosed with histologically confirmed EOG or periodontitis from 1997 to 2022. Information such as medical history, lifestyle factors, clinical presentation, radiographic and histopathologic features were included for 27 client-owned cats. Response to treatment and long-term follow-up was also recorded., Results: Moderate-to-severe periodontal disease was radiographically confirmed in 78% (21/27) of cats with moderate-to-severe EOG, compared with the evidence of periodontal disease noted in 30% (8/27) of cases during awake oral examination. Horizontal bone loss, along with missing teeth, were the predominant radiographic features noted in 89% (24/27) of cases. The predominant histopathologic feature was moderate-to-severe, erosive-to-ulcerative, neutrophilic and lymphoplasmacytic inflammation with varying degrees of epithelial and stromal hyperplasia. Two cats developed feline chronic gingivostomatitis (FCGS)-like lesions, and seven cats exhibited worsening of aggressive periodontitis (AP). Lack of improvement in the severity of gingivitis or clinical signs evident at the first follow-up appointment was significantly associated with progression of disease ( P  = 0.004)., Conclusions and Relevance: The results of this study demonstrate the importance of oral evaluations in cats as early as 6 months of age. For cats exhibiting substantial gingivitis, an anesthetized evaluation, periodontal treatment and long-term monitoring are recommended. Given the high frequency of moderate-to-severe periodontitis encountered in these cats, clients should be informed about the potential need for tooth extractions. EOG may progress to AP. Finally, this study suggests that there could be a link between EOG and FCGS; however, further studies are needed to better characterize this condition and establish any potential link between the two entities.

Objectives: The aim of this pilot study was to determine the safety, efficacy and immunomodulatory function of systemically administered adipose-derived mesenchymal stem cells (ASCs) in cats affected by feline chronic gingivostomatitis (FCGS) prior to full-mouth tooth extractions., Methods: Five client-owned cats affected with FCGS that did not undergo full-mouth tooth extractions for FCGS treatment received two intravenous injections of 20 million fresh, allogeneic or autologous ASCs. An oral examination with photographs, a complete blood count, blood immune cell phenotyping and a biochemical profile were completed at 0 and 6 months after treatment., Results: Four cats completed the study and one cat exited the study 3 months after treatment. While the treatment was determined to be clinically safe, no positive clinical response was observed in three cats and a mild response was noted in two cats. Furthermore, none of the cats exhibited immune modulation, as evidenced by no alteration in circulating CD8 + T cells, normalization of the CD4:CD8 ratio or neutrophil counts., Conclusions and Relevance: Unlike the reported efficacy of ASCs in treating cats with non-responsive FCGS after full-mouth tooth extraction, the systemic administration of ASCs prior to full-mouth tooth extraction lacks substantial clinical efficacy and is not recommended at this time.

Objective: To identify associations between microbes and host genes in cats with feline chronic gingivostomatitis (FCGS), a debilitating inflammatory oral mucosal disease with no known cause, compared with healthy cats and cats with periodontitis (control cats)., Animals: 19 control cats and 23 cats with FCGS., Procedures: At least 1 caudal oral mucosal swab specimen was obtained from each cat. Each specimen underwent unbiased metatranscriptomic next-generation RNA sequencing (mNGS). Filtered mNGS reads were aligned to all known genetic sequences from all organisms and to the cat transcriptome. The relative abundances of microbial and host gene read alignments were compared between FCGS-affected cats and control cats and between FCGS-affected cats that did and did not clinically respond to primary treatment. Assembled feline calicivirus (FCV) genomes were compared with reverse transcription PCR (RT-PCR) primers commonly used to identify FCV., Results: The only microbe strongly associated with FCGS was FCV, which was detected in 21 of 23 FCGS-affected cats but no control cats. Problematic base pair mismatches were identified between the assembled FCV genomes and RT-PCR primers. Puma feline foamy virus was detected in 9 of 13 FCGS-affected cats that were refractory to treatment and 5 healthy cats but was not detected in FCGS-affected cats that responded to tooth extractions. The most differentially expressed genes in FCGS-affected cats were those associated with antiviral activity., Conclusions and Clinical Relevance: Results suggested that FCGS pathogenesis has a viral component. Many FCV strains may yield false-negative results on RT-PCR-based assays. Coinfection of FCGS-affected cats with FCV and puma feline foamy virus may adversely affect response to treatment.

Feline chronic gingivostomatitis is a frustrating disease to manage owing to its elusive etiopathogenesis and its subsequently suboptimal treatment options. Nevertheless, efforts to shed light on the disease over the past few decades have advanced the knowledge on its potential etiopathogenesis and the success rates of available treatment options. Further research is ongoing, with promising attempts to better understand and treat this, likely, multifactorial disease., Competing Interests: Disclosure The authors have no financial disclosures to acknowledge., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Squamous cell carcinoma is the most common oral cancer in the cat and presents as a locally aggressive lesion for which an effective therapeutic protocol remains elusive. Feline oral squamous cell carcinoma (OSCC) shares many clinical characteristics with human head and neck squamous cell carcinoma (HNSCC). Accordingly, present studies were conducted to determine similarities for immune markers shared by feline OSCC and human HNSCC. Biopsies harvested from a feline patient cohort-1 (n = 12) were analyzed for lymphoid cell infiltrates by immunohistochemistry (IHC). Results revealed unique patterns of T cell infiltration involving both neoplastic epithelium and stroma that were detected in most patient tumor biopsies (92%) examined by IHC staining for CD3. Intratumoral B cell infiltrates were detected within tumor stroma only, based on IHC staining for CD79a and CD20 for all patients within the same cohort-1. Infiltration of tumors by a regulatory CD4 T cell subset (Tregs) defined by expression of the forkhead transcription factor FoxP3, was also detected in biopsies from 57% of patients and involved infiltration of neoplastic epithelium and stroma. Patient biopsies were also examined for expression of immunomodulator cyclooxygenase (COX)-2 and revealed positive but weak staining of neoplastic epithelium in a significant proportion of cases (75%). Interestingly, COX-2 expression was detected in both neoplastic epithelium and stroma. Blood collected from a second cohort of feline OSCC patients (n = 9) revealed an increased frequency of circulating CD4+FoxP3+ T cells when compared to healthy adult controls (n = 7) (P = 0.045), although frequencies of CD4+CD25+FoxP3+ T cells were comparable between patients and healthy pet cat controls. Lastly, biopsies from feline OSCC patients were characterized for histologic subtype using a classification scheme previously described for human HNSCC. This analysis revealed the conventional subtype as the predominant variant (75%) with conventional subtypes split evenly between well differentiated and moderately differentiated carcinomas. Two cases were classified as papillary and one case as basaloid subtypes. Correlations between subtype, immune marker scores or circulating Treg frequencies and clinical characteristics or outcome were not detected, most likely due to small patient numbers within patient cohorts. However, findings from these studies provide a preliminary step in the characterization of immune and histologic markers that will be critical to defining prognostic immune markers for feline OSCC and potential targets for testing of immunotherapeutics also relevant to human HNSCC in future studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

OBJECTIVE To describe the radiographic outcome of root canal treatment (RCT) of canine teeth of cats. DESIGN Retrospective case series. ANIMALS 32 cats with 37 canine teeth with complicated crown fractures that underwent RCT. PROCEDURES Medical record databases of 5 referral veterinary hospitals were searched to identify cats that underwent RCT between 1998 and 2016. Only cats that had at least 1 follow-up examination during which radiographs were obtained of the treated canine tooth or teeth were included in the study. Dental radiographs obtained before and immediately after RCT and during all follow-up examinations were reviewed. Treatment was considered successful if the periodontal ligament space was within reference limits and preoperative external inflammatory root resorption (EIRR), if present, had stabilized. Treatment was considered to have no evidence of failure if preoperative EIRR had stabilized and preexisting periapical lucency was stable or decreased in size but had not resolved. Treatment was considered to have failed if periapical lucency or EIRR developed subsequent to RCT or preexisting periapical lucency increased in size or preoperative EIRR progressed following RCT. RESULTS Follow-up time after RCT ranged from 3 to 72 months. The RCT was successful for 18 (49%) of the 37 treated teeth, had no evidence of failure for 12 (32%), and failed for 7 (19%). Preexisting EIRR and patient age ≥ 5 years significantly increased the rate of RCT failure. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that RCT was a viable treatment option to salvage endodontically diseased canine teeth in cats.

Objective: To describe the application of 3-dimensional (3D) printing in advanced oral and maxillofacial surgery (OMFS) and to discuss the benefits of this modality in surgical planning, student and resident training, and client education., Study Design: Retrospective case series., Animals: Client-owned dogs (n = 28) and cats (n = 4) with 3D printing models of the skulls., Methods: The medical records of 32 cases with 3D printing prior to major OMFS were reviewed., Results: Indications for 3D printing included preoperative planning for mandibular reconstruction after mandibulectomy (n = 12 dogs) or defect nonunion fracture (n = 6 dogs, 2 cats), mapping of ostectomy location for temporomandibular joint ankylosis or pseudoankylosis (n = 4 dogs), assessment of palatal defects (n = 2 dogs, 1 cat), improved understanding of complex anatomy in cases of neoplasia located in challenging locations (n = 2 dogs, 1 cat), and in cases of altered anatomy secondary to trauma (n = 2 dogs)., Conclusion: In the authors' experience, 3D printed models serve as excellent tools for OMFS planning and resident training. Furthermore, 3D printed models are a valuable resource to improve clients' understanding of the pet's disorder and the recommended treatment., Clinical Relevance: Three-dimensional printed models should be considered viable tools for surgical planning, resident training, and client education in candidates for complex OMFS., (© 2017 The American College of Veterinary Surgeons.)

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., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Clefts of the primary palate in the dog are uncommon, and their repair can be challenging. The aims of this article are to provide information regarding pathogenesis and convey practical information for the repair of these defects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A 16-year-old spayed female cat was evaluated for lagophthalmos and chronic exposure keratitis in both eyes. Ophthalmic examination revealed upper and lower eyelid entropion of the left eye (OS) and markedly decreased retropulsion, restricted eye movement, marked episcleral congestion, and severe keratitis of both eyes (OU). Magnetic resonance imaging of both orbits revealed extensive, irregular, contrast-enhancing tissue without evidence of osteolysis considered compatible with diffuse inflammatory tissue. Feline herpesvirus DNA was not detected in conjunctival samples. Partial temporary tarsorrhaphies were placed OU, and the cat was treated with topically administered erythromycin ointment OU, orally administered famciclovir and prednisolone, and sublingually administered buprenorphine. Little improvement was noted after 2 weeks. Six weeks after initial presentation, a left exenteration was performed and histopathology was consistent with idiopathic sclerosing orbital pseudotumor (ISOP). Ten weeks after initial presentation, the patient represented for weight loss and jaw pain. Computed tomography demonstrated disease progression in the right orbit and the patient was euthanized. Histopathology of the decalcified skull revealed an aggressive and highly infiltrative mass involving the right orbit with extension to the maxilla, hard palate, nasal cavity and gingiva most consistent with feline restrictive orbital myofibroblastic sarcoma (FROMS). Clinical data from this patient support the reclassification of ISOP as FROMS. MRI and CT may provide supportive evidence for FROMS, but histopathology is necessary for definitive diagnosis. Aggressive and early surgical treatment, including bilateral exenteration, with adjunctive radiotherapy and/or chemotherapy should be considered for patients with FROMS., (© 2013 American College of Veterinary Ophthalmologists.)

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).

Objective-To describe clinical features of oral and maxillofacial osteomas in cats. Design-Retrospective case series. Animals-7 cats with oral or maxillofacial osteoma or both. Procedures-Medical records were reviewed for information on signalment, history, clinical signs, physical examination findings, diagnostic imaging findings, results of serum biochemical analyses and histologic testing, surgical procedures performed, and perioperative complications. Outcome was determined on the basis of follow-up telephone interviews of owners. Results-Cats ranged from 1 to 23 years of age. Clinical signs were observed in 5 cats and were attributed to the presence of the mass. Diagnostic imaging (radiography and computed tomography) and histologic examination confirmed the diagnosis of osteoma. Three cats were euthanatized; 1 cat was treated by mandibulectomy, 1 was treated by maxillectomy, and 2 were treated by debulking. At the time of follow-up at least 1 year after surgery, all 4 treated cats were alive, with owners reporting an acceptable quality of life. Conclusions and Clinical Relevance-Osteoma of the oral and maxillofacial regions is an uncommon tumor in cats. Most cats are examined during an advanced stage of the disease, when treatment options may be limited. Although osteoma is a benign tumor, the recommendation is to perform a clinical evaluation, diagnostic imaging, biopsy, and treatment early in the disease process, when less invasive surgical approaches may be feasible.

Squamous cell carcinoma is the most common oral cancer in the cat and presents as a locally aggressive lesion for which an effective therapeutic protocol remains elusive. Feline oral squamous cell carcinoma (OSCC) shares many clinical characteristics with human head and neck squamous cell carcinoma (HNSCC). Accordingly, present studies were conducted to determine similarities for immune markers shared by feline OSCC and human HNSCC. Biopsies harvested from a feline patient cohort-1 (n = 12) were analyzed for lymphoid cell infiltrates by immunohistochemistry (IHC). Results revealed unique patterns of T cell infiltration involving both neoplastic epithelium and stroma that were detected in most patient tumor biopsies (92%) examined by IHC staining for CD3. Intratumoral B cell infiltrates were detected within tumor stroma only, based on IHC staining for CD79a and CD20 for all patients within the same cohort-1. Infiltration of tumors by a regulatory CD4 T cell subset (Tregs) defined by expression of the forkhead transcription factor FoxP3, was also detected in biopsies from 57% of patients and involved infiltration of neoplastic epithelium and stroma. Patient biopsies were also examined for expression of immunomodulator cyclooxygenase (COX)-2 and revealed positive but weak staining of neoplastic epithelium in a significant proportion of cases (75%). Interestingly, COX-2 expression was detected in both neoplastic epithelium and stroma. Blood collected from a second cohort of feline OSCC patients (n = 9) revealed an increased frequency of circulating CD4+FoxP3+ T cells when compared to healthy adult controls (n = 7) (P = 0.045), although frequencies of CD4+CD25+FoxP3+ T cells were comparable between patients and healthy pet cat controls. Lastly, biopsies from feline OSCC patients were characterized for histologic subtype using a classification scheme previously described for human HNSCC. This analysis revealed the conventional subtype as the predominant variant (75%) with conventional subtypes split evenly between well differentiated and moderately differentiated carcinomas. Two cases were classified as papillary and one case as basaloid subtypes. Correlations between subtype, immune marker scores or circulating Treg frequencies and clinical characteristics or outcome were not detected, most likely due to small patient numbers within patient cohorts. However, findings from these studies provide a preliminary step in the characterization of immune and histologic markers that will be critical to defining prognostic immune markers for feline OSCC and potential targets for testing of immunotherapeutics also relevant to human HNSCC in future studies.

Introduction: Digital tomosynthesis (DT) has emerged as a potential imaging modality for evaluating anatomic structures in veterinary medicine. This study aims to validate the diagnostic yield of DT in identifying predefined anatomic structures in feline cadaver heads, comparing it with conventional intraoral dental radiography (DR). Methods: A total of 16 feline cadaver heads were utilized to evaluate 19 predefined clinically relevant anatomic structures using both DR and DT. A semi-quantitative scoring system was employed to characterize the ability of each imaging method to identify these structures. Results: DT demonstrated a significantly higher diagnostic yield compared to DR for all evaluated anatomic structures. Orthogonal DT imaging identified 13 additional anatomic landmarks compared to a standard 10-view feline set obtained via DR. Moreover, DT achieved statistically significant higher scores for each of these landmarks, indicating improved visualization over DR. Discussion: These findings validate the utility of DT technology in reliably identifying clinically relevant anatomic structures in the cat skull. This validation serves as a foundation for further exploration of DT imaging in detecting dentoalveolar and other maxillofacial bony lesions and pathologies in cats. [ABSTRACT FROM AUTHOR]

UnlabelledMesenchymal 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.SignificanceThis 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.

Gingiva-derived mesenchymal stromal cells (GMSCs) are multipotent cells characterized by multilineage differentiation potential, proliferative expansion, and unique immunomodulatory ability, making them attractive as a new treatment of periodontal regeneration. In this study, GMSCs obtained from the gingiva of healthy cats (HE) as well as from cats affected by tooth resorption (TR) were isolated and characterized. Feline GMSCs (fGMSCs) from HE patients exhibited fibroblast-like morphology, developed cellular body, specific growth pattern, high expansion, and proliferative potential as well as reduced senescence signature. fGMSCs demonstrated high s-100 and IL-10 positive cells, while simultaneously having low activity of IL-1. Moreover, high activity of ki-67 combined with reduced senescence markers were noted. In comparison, GMSCs from cats with TR exhibited enlarged nuclei and flat, irregular shape along with increased expression of CD44, s-100 and CD45 and downregulation of CD73. GMSCs from TR cats showed lower ability to form colonies, increased incidence of apoptosis, higher number of senescent cells, and reduced cell migration. Upregulation of pro-inflammatory cytokines was also noted in the TR group along with lower expression of mTOR and miR-17 and upregulation of miR-378. Mitochondrial dynamics, biogenesis and antioxidant properties are also negatively impacted in this group. Collectively, our findings suggest that GMSCs isolated from the gingiva of cats affected with TR have deteriorated functionality caused by impaired proliferation and growth and possibly mediated via mitochondrial dysfunction. fGMSCs or their EV's should be further investigated for their role in the pathophysiology of TR in cats. [ABSTRACT FROM AUTHOR]