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To report the outcomes of cats that underwent surgical correction for sialoceles. Multi-institutional retrospective cohort study. Twenty-one client-owned cats. Medical records were examined of cats diagnosed with sialocele, which underwent surgical intervention over an 11-year period at one of 10 referral hospitals. The data collected included signalment, clinical signs, diagnostic imaging, histopathology, surgical procedures performed, and postoperative complications. The most common presenting complaints for cats with sialocele included dysphagia and ptyalism. Only two cats had a recent history of trauma, and one was diagnosed with a concurrent sialolith. Most displayed visible tissue swelling, with ranulae being most common. Surgical treatment consisted of sialoadenectomy and/or marsupialization. Intraoperative complications occurred in three cats, and postoperative complications in five cats. No recurrence or development of contralateral sialoceles were reported during the follow-up period (30-968 days). The majority of cats did not have a clear underlying cause for developing a sialocele. The sublingual and mandibular salivary glands were presumed to be the most commonly affected. Mandibular and sublingual sialoadenectomy and/or marsupialization provided resolution of clinical signs to the 21 cats that underwent these procedures. Sialocele, although rare, should remain a differential diagnosis when managing cats with relevant clinical signs. Surgical intervention appears to offer resolution of signs with apparently low overall risk of complication or short-term recurrence. In cats it is necessary to evaluate whether sialoadenectomy is necessary, or whether marsupialization alone should be attempted as a less invasive first-line surgical intervention.

ObjectiveTo evaluate the kinematics and stability of the temporomandibular joint (TMJ) of cats and dogs with and without a TMJ replacement (TMJR) prosthesis under simulated bite forces and mouth opening.AnimalsSixteen cadaver skulls from domestic cats (n = 8) and medium- to large-breed dogs (n = 8).MethodsIntact TMJs were tested. Following condylectomy and coronoidectomy, the skulls were fitted with a TMJR prosthesis unilaterally and retested. Prosthesis was similarly implanted in the contralateral TMJ in 4 cats and 4 dogs before retesting. Left and right bite motions were evaluated before bite contact to peak bite force (200 N in dogs, 63 N in cats). Mouth opening motion was recorded. Mandibular displacement under load was evaluated in 3 orthogonal planes. Maximal displacement was compared between TMJR groups and native TMJ. Prosthesis-bone motion of the temporal and mandibular components was evaluated during simulated bites and mouth opening.ResultsTMJR resulted in joint motion not demonstrably different from the native TMJ, with the ability to fully open and close the mouth and with minimal laterotrusion. The TMJR prosthesis demonstrated similar stability after unilateral and bilateral replacement during bite force and with an open mouth. Mean implant-bone motion during bite simulations for the temporal and mandibular TMJR components was ≤ 60 µm in cats and ≤ 30 µm in dogs.Clinical relevanceA novel TMJR can be implanted and allows normal jaw motion. Joint stability is maintained after TMJR implantation in the TMJ of dogs and cats TMJ that is devoid of muscular support.

ObjectiveExtracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are promising avenues in regenerative medicine, offering unique immunomodulatory and regenerative properties with lower immunogenicity. This study delves into the distinctive features of EVs extracted from feline adipose-derived MSCs (ASCs) and placenta-derived MSCs (PMSCs). The tissues were collected from 11 female cats aged between 4 and 7 years old.SampleEVs extracted from MSCs from discarded fetal membranes from 7 female cats and SC adipose tissue from 11 cats.MethodsWe comprehensively explored morphological characteristics, mitochondrial density, surface markers, and pro- and anti-inflammatory mediators, uncovering notable differences between ASCs and PMSCs.ResultsMorphologically, ASCs exhibit a spindle-shaped form in contrast to the spherical morphology of PMSCs. Proliferation and clonogenic potential assessments reveal the faster proliferation and robust clonogenic nature of ASCs, suggesting their potential vital role in regenerative processes. Surface marker expression analysis indicates a significantly higher expression of multipotency-associated markers in ASCs, suggesting their superior proregenerative potential. Phenotyping of EVs demonstrates distinctive features, with CD9 expression suggesting varied EV secretion patterns. Notably, PMSCs exhibit superior CD81 expression, indicating their potential as preferred donors of mitochondria. Pro- and anti-inflammatory mediators analyzed at mRNA and microRNA levels reveal higher RNA content in EVs compared to source cells, emphasizing the potential of EVs in directing regenerative processes. Differential microRNA expression in EVs derived from ASCs hints at their regulatory roles in anti-inflammatory and immunometabolic processes.Clinical relevanceThis study lays a foundation for understanding the nuances between ASCs and PMSCs, which is crucial for harnessing the full therapeutic potential of MSCs and their EVs in tissue repair and regeneration.

Feline chronic gingivostomatitis (FCGS) is a debilitating inflammatory oral mucosal disease with a multifactorial etiology. The clinical diagnosis of FCGS is made based on inspection of severe inflammatory lesions and histological confirmation rather than a molecular diagnostic outcome. This gap limits the ability to provide an early diagnosis. In this report, we seek to provide additional diagnostic tools using genomics to aid in providing clinically relevant information. The use of in-depth diagnostic tools, like transcriptomics of diseased tissues, to diagnose FCGS and stratify patients into predictive treatment response groups would dramatically improve both clinical decisions and patient outcomes. In this study, we addressed the gap in diagnostic options using transcriptomic analysis of caudal oral mucosal swab specimens coupled to detailed medical record linkage of FCGS-affected cats undergoing tooth extractions and in some cases administration of mesenchymal stromal cells (MSCs). To better identify markers of disease and potential response to treatment, the transcriptomes of FCGS-afflicted cats were compared to those of healthy cats and those with chronic periodontitis to clearly establish diagnostic biomarker signal transduction connections. Phosphatidylinositol 3-kinase/Ak strain transforming (PI3K/AKT) and stress-activated protein kinases/Jun N-terminal kinase (SAP/JNK) signaling pathways were significantly differentially regulated in FCGS-afflicted cats. Activation of these pathways also differed in the treatment response groups. In conjunction, the enzymes Caspase 4 (CASP4), matrix metalloproteinase-8 (MMP8), and prostaglandin-endoperoxide synthase 2 (PTGS2) were identified as potential biomarkers for the prediction of treatment response outcomes. The observations in the case study support the use of transcriptomics of FCGS patients to contribute to improved molecular diagnostics for the diagnosis and treatment of FCGS.

Odontodysplasia is an uncommon dental developmental disorder associated with enamel, dentin, pulp abnormalities, and overall tooth morphology. The affected tooth is grossly abnormal in size and contour and is commonly associated with swelling of the affected area and failure of eruption. Histologically, the enamel and dentin are hypoplastic and hypomineralized. Odontodyplasia occurs most commonly in response to direct trauma to the developing tooth bud (enamel organ and dental follicle). Data on the prevalence and features of non-traumatic odontodysplasia are lacking. Medical records of dogs diagnosed with odontodysplasia were reviewed at the William R. Pritchard Veterinary Medical Teaching Hospital (VMTH), University of California, Davis, for 10 years (from 2013 to 2023). Dogs with a known history of facial trauma, persistent deciduous tooth or teeth over the region of odontodysplastic tooth or teeth, and endodontic disease of the persistent deciduous tooth or teeth were excluded from the study. Twenty-eight dogs were included in this retrospective study, representing an incidence of 1.4 per 100 dogs presenting over 10 years. Regional odontodysplasia (RO) was identified in twenty-two dogs, and generalized odontodysplasia (GO) was found in six dogs. Both comprehensive oral examination and diagnostic imaging were essential in diagnosing and assessing the presence of odontodysplasia. Awake oral examination failed to identify odontodysplasia in almost 70% of the RO cases. Secondary diseases or lesions in odontodysplastic teeth, such as periodontal disease, endodontal disease, and perio-endo lesions, were commonly seen and were particularly more frequently identified in strategic teeth (canine and carnassial teeth) than non-strategic ones. Similarities, such as female predilection, maxilla more commonly affected, and clinical signs, were observed between RO in dogs and those reported in people. The exact etiology of non-traumatic odontodysplasia remains elusive, and the condition may be of multifactorial causality.

IntroductionDigital 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).MethodsA 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.ResultsDT 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.DiscussionThese 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.

OBJECTIVE: This study aims to report the surgical and medical management of generalized chronic maxillofacial infection with multiple intra- and extraoral draining tracts in a dog. CASE SUMMARY: A 6 years-old, male neutered pit bull terrier dog underwent a staged procedure. First, a diagnostic work-up including hematologic and biochemical analysis, conventional computed tomography (CT) with contrast of the skull, and a rhinoscopic evaluation of the draining tracts was performed. Samples were obtained for histopathological, microbial, and fungal testing. Second, a 4 week course of antimicrobials based on culture and sensitivity results was administered. Third, an extraoral approach to soft tissue reconstruction was accomplished as a first stage in the repair process. Finally, an intraoral approach to repair the oronasal fistulous draining tracts was performed. A 6 months follow-up skull CT revealed various stages of repair and remodeling and adequate soft tissue healing. CLINICAL RELEVANCE: A staged procedure is a suitable option to treat chronic and generalized frontal and maxillary infection with multiple intra- and extraoral fistulous draining tracts in dogs.

ObjectiveDetermine diagnostic yield of chest, abdomen, and 4-site screening to diagnose metastatic disease and secondary diseases of prognostic significance in dogs with oral cancer.SampleMedical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.ResultsThoracic metastasis was diagnosed in 4.9% (0.9% odontogenic, 6.5% nonodontogenic) of oral tumors. Oral malignant melanoma and multilobular osteochondrosarcoma were most at risk. Abdominal metastasis was diagnosed in 2% of oral tumors (0% odontogenic, 3.1% nonodontogenic) and cytologically confirmed in 2 cases (0.6% [2/295)] of all abdominal ultrasounds (AUS) 5.5% [2/36] of all AUS that had cytology). Both cases had oral malignant melanoma. Incidental disease was diagnosed in 53.1% and 81.3% of thoracic and abdominal screenings, respectively. Major findings were more common in AUS (7.8%) compared to thoracic screening (1.9%). The prevalence of incidental findings was similar for odontogenic and nonodontogenic tumors. Both metastasis and major findings were diagnosed more commonly with thoracic CT compared to radiographs. Metastasis or a major finding of prognostic significance was diagnosed in at least 1 test in 27.8% of patients that had head CT, lymph node cytology, thoracic screening, and AUS (n = 115).Clinical relevanceMajor incidental findings were more commonly detected with AUS and were diagnosed in 1 in every 12 patients. However, metastatic disease was most commonly detected with thoracic screening. When all 4 screening tests are performed, there is an approximately 1 in 4 chance of diagnosing metastasis or major significant disease regardless of tumor type.

ObjectiveDetermine locoregional diagnostic yield of 4-site screening (head, neck, chest, and abdomen) to diagnose metastatic disease or clinically significant comorbid diseases in dogs with oral cancer.Animals381 dogs with histologically confirmed oral tumors.MethodsMedical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.ResultsSkull and neck CT scan was performed on 348 patients. Bone lysis was present in 74.4% of tumors. Oral squamous cell carcinoma, sarcomas, and T2-T3 (> 2 cm) tumors had a significantly (P < .05) increased incidence of lysis compared to odontogenic and T1 (< 2 cm) tumors, respectively. Minor incidental findings were present in 60.6% of CT scans. Major incidental findings were found in 4.6% of scans. The risk of diagnosing an incidental finding increased by 10% and 20% per year of age for minor and major findings, respectively. Lymph node metastasis was diagnosed with CT or cytology in 7.5% of cases (10.7% of nonodontogenic tumors, 0% of odontogenic tumors). Oral malignant melanoma, oral squamous cell carcinoma, and T3 tumors had the highest prevalence of metastatic disease at the time of staging. The presence of bone lysis was not associated with cervical metastasis.Clinical relevanceMajor incidental findings were rare (< 5%) but primarily included secondary extraoral tumors. Lymphatic metastasis was diagnosed in 10.7% of nonodontogenic tumors, but cytology was not performed in the majority of cases and often included only a single mandibular node. Therefore, these results likely underestimate the incidence of lymphatic metastasis. Guided lymph node sampling is highly recommended, especially for oral malignant melanoma, squamous cell carcinoma, and T2-T3 tumors.

This study explored the feasibility of using fish skin bandages as a therapeutic option for third-degree skin burns. Following the California wildfires, clinical observations of animals with third-degree skin burns demonstrated increased comfort levels and reduced pain when treated with tilapia fish skin. Despite the promises of this therapy, there are few studies explaining the healing mechanisms behind the application of tilapia fish skin. In this study, mice with third-degree burns were treated with either a hydrocolloid adhesive bandage (control) (n = 16) or fish skin (n = 16) 7 days post-burn. Mice were subjected to histologic, hematologic, molecular, and gross evaluation at days 7, 16, and 28 post-burn. The fish skin offered no benefit to overall wound closure compared to hydrocolloids. Additionally, we detected no difference between fish skin and control treatments in regard to hypermetabolism or hematologic values. However, the fish skin groups exhibited 2 times more vascularization and 2 times higher expression of antimicrobial defensin peptide in comparison to controls. Proteomic analysis of the fish skin revealed the presence of antimicrobial peptides. Collectively, these data suggest that fish skin can serve as an innovative and cost-effective therapeutic alternative for burn victims to facilitate vascularization and reduce bacterial infection.

Internal distraction devices are commonly used in congenital micrognathia. The eventual need for device and screw removal can be challenging, requiring extensive dissection and disturbance of bone regenerate. Bioabsorbable poly-L-lactide (PLLA) screws, compared to traditional titanium screws, simplify device removal. Previous in vivo studies have found that the maximal compressive force generated by mandibular distraction is 69.4N. We hypothesized that PLLA screws could support these compressive/distraction forces. Ten mandibles were obtained from 5 canine cadavers. Paired mandibles from the same cadaver were each fixated to a mandibular distractor with eight screws (either titanium or PLLA). Devices were each set to 15 and 30 mm of distraction distance. Compression force of 80 N was then generated parallel to the axis of the distraction device. Distractor displacement was measured to detect any mechanical failure during this pre-set load. Finally, if no failure was observed at 80 N, a load-to-failure compression test was done in the PLLA group to determine the mechanical failure point. All distractors in both the titanium and PLLA screw groups withstood 80 N of compression without failure. When the load-to-failure test was performed in the PLLA group, the average device failure point was 172.8 N (range 148-196 N). Review of high-frame-rate video demonstrated that all failures occurred due to the PLLA screws breaking or falling out. Bioabsorbable PLLA screws can withstand compressive forces more than double that of the maximal in vivo forces needed during mandibular distraction. These screws may be an acceptable alternative for the fixation of internal mandibular distractors.

ObjectiveThis study aimed to characterize the clinical and histopathologic features of oral eosinophilic lesions in cats.Animals38 client-owned cats.MethodsThe 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.ResultsThe 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 relevanceThe 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 relevanceFeline 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 optionsLocalized 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.AimsThis review outlines current and emerging concepts linking available science pertaining to FCGS and clinical management of the disease.Evidence baseThe 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.

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.

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.

The study of past pathologies by means of quantitative reports is an underexplored approach to deal with the biology and ecology of extinct taxa. In the present study, we assessed the prevalence rate of primary osteoarthritis in a large sample of Prolagus sardus (Mammalia, Lagomorpha) from Medusa Cave (also known as Grotta Dragonara, Sardinia, Italy; Late Pleistocene) to shed light on the evolutionary history of small mammals under isolation regimes. The hip and knee joints of 246 femora were examined grossly, microscopically, and using advanced radiology, recording essential biological features such as age or weight. We noted that 27.7% of skeletally mature sample had degenerative disorder of the joints, with higher frequency in adults (p-value < 0.05), regardless of their body mass (p-value > 0.05). Histologically, affected joints displayed changes in subchondral plate potentially reflecting adaptive modeling. Our analysis revealed ageing (the extended lifespan) as the main driver of this prevalence rate, whereas mechanical factors (caused by a particular lifestyle) were considered of significantly lesser importance. Our results provide additional empirical support to the analytical framework of life history theory from a new perspective, according to which, under low extrinsic mortality regimes, selection should favor slow-strategies (extended lifespan) in small-sized mammals.

Museum skull specimens from 224 Arctic foxes (Vulpes lagopus) were examined macroscopically using an established protocol for examination of mammalian skull specimens. Foxes were collected from coastal and island regions of Alaska, USA, except for two individuals. Collection years ranged from 1931 to 2016 with most specimens collected during the 1950s and 1960s. The study population comprised more females (n = 134, 59.8%) than males (n = 83, 37.0%) and individuals of unknown sex (n = 7, 3.1%). There were 108 (48.2%) young adults, 115 (51.3%) adults, and one (0.4%) individual of unknown age. A total of 8,891 teeth (94.5%) were available for examination. The most common types of pathology observed were periodontitis (n = 222, 99.1%), dental fractures (n = 175, 78.1%) and attrition/abrasion (n = 198, 88.4%). Periapical lesions (n = 12, 5.3%), temporomandibular joint (TMJ) osteoarthritis (n = 3, 1.3%) and root number variation (n = 5, 2.2%) were less common. Enamel hypoplasia was noted in eight foxes (3.6%), all of which were discovered on St. Matthew Island, Alaska, in 1963. As in other canid species, periodontitis, attrition/abrasion and tooth fractures are common in the Arctic fox, while TMJ pathology is rare. Loss of tooth crown substance probably reflects the influence of diet, interspecific and conspecific aggression and oral trauma due to trapping and hunting methods. The high prevalence of periodontitis is probably also due to the combined effects of diet, genetics and host immune reaction to oral bacteria.

ObjectiveTo describe an intraoral approach (IOA) for zygomatic sialadenectomy in dogs and to compare this surgical approach to a modified lateral orbitotomy approach (LOA).Study designCadaveric study and short case series.Sample populationTen canine cadavers and three dogs with clinical disease.MethodsBilateral zygomatic sialoadenectomies were performed in six mesocephalic, two brachycephalic and two dolichocephalic cadavers, randomly assigned to IOA on one side and LOA on the contralateral side. Duration of surgery, ease of surgical stage scores (rated on 5-point Likert scale) and completeness of gland removal were recorded. Additionally, IOA was performed in three dogs with zygomatic salivary gland (ZSG) disease.ResultsRemoval of the ZSG was complete in 8/10 and 10/10 dogs using the IOA and LOA, respectively. Surgery was faster with IOA (42.0 min; 33.5-49.6 min) than LOA (65.7 min; 54.9-76.4 min, p = .005). Ease of removal did not differ between approaches (p = .091). Diseased ZSGs were successfully removed in three dogs without intra- or short-term postoperative complications.ConclusionsThe intraoral approach described here was technically equally challenging but faster than the LOA. Its clinical use led to an uneventful surgery with excellent short-term outcome in three dogs.Clinical relevanceThe IOA provides an alternative approach for zygomatic sialoadenectomy in dogs with ZSG disease.

Spontaneous repair and remodeling of the mandibular head of the condylar process is a rarely reported outcome following condylectomy. This clinical report describes the spontaneous repair and subsequent remodeling of the mandibular head of the condylar process in four immature dogs that sustained traumatic injuries, necessitating surgical intervention through arthroplasty via partial or complete condylectomy, or caudal mandibulectomy. In subsequent evaluations, it was observed that all dogs exhibited clinically functional TMJs, as evidenced by an appropriate range of motion. These findings were corroborated by the owners reports of the patients normal eating and drinking abilities. Conventional and cone-beam computed tomography studies demonstrated the repair and remodeling of the osseous tissues of the mandibular head of the condylar process. Histopathology was unavailable to assess the novel tissues. No evidence of intraarticular or extraarticular ankylosis or osteoarthritic changes was observed.

IntroductionMesenchymal stromal cells (MSC) therapy has emerged as a potential treatment option for refractory FCGS. However, there is a lack of long-term data on the use of MSC therapy in cats. This study aimed to evaluate the long-term safety and efficacy of MSC therapy for FCGS and investigate potential factors associated with treatment outcomes.MethodsThis study was a retrospective evaluation of 38 client-owned cats with refractory FCGS who received MSC therapy. Medical records, histopathology, and the Stomatitis Activity Disease Index (SDAI) were reviewed. Correlations of the long-term follow-up success rates with SDAI and cell line type used were conducted. A client survey was also performed to assess side effect occurrence, quality-of-life following treatment, and overall treatment satisfaction.ResultsLong-term follow-up ranged from 2 to 9 years post-MSC treatment. The overall positive response rate to MSC treatment was 65.5%, with 58.6% of cats exhibiting permanent improvement or cure. Adverse effects occurring during or immediately after treatment were noted in 34.2% of cases, the majority being transient, self-resolving transfusion-like reactions. No long-term adverse events were noted. No significant correlation in outcome was detected between allogeneic and autologous MSC treatment (p = 0.871) or the severity of the SDAI at entry (p = 0.848) or exit (p = 0.166), or the delta SDAI between entry and exit (p = 0.178). The status 6 months (none to partial improvement vs. substantial improvement to resolution) post-therapy was a predictor of long-term response (value of p

ObjectivesThis study aimed to characterize the clinical, radiographic and histopathologic features of early-onset gingivitis (EOG) and periodontitis in cats.MethodsThe 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.ResultsModerate-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 relevanceThe 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.

Objective The aim of this study was to assess bone density, bone architecture and clinical function of canine nonunion distal appendicular long bone fractures with a defect treated with fixation, compression-resistant matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2).Study design Prospective cohort study with dogs at least 1-year post treatment. Computed tomography was performed and quantitative measurements from previous fracture sites were compared with measurements from contralateral limbs. Subjective evaluation included gait assessment and palpation.Results Six patients met the inclusion criteria. The rhBMP-2 treated bone exhibited higher density at the periphery and lower density in the centre, similar to the contralateral limb. All patients were weight bearing on the treated limb and all fractures were healed.Conclusion The rhBMP-2-treated bone underwent restoration of normal architecture and density. Acceptable limb function was present in all patients. The results of this study can serve as a basis for long-term response in treating nonunion fractures in veterinary patients.

The increasing prevalence of degenerative cartilage disorders in young patients is a growing public concern worldwide. Cartilage's poor innate regenerative capacity has inspired the exploration and development of cartilage replacement treatments such as tissue-engineered cartilages and osteochondral implants as potential solutions to cartilage loss. The clinical application of tissue-engineered implants is hindered by the lack of long-term follow-up demonstrating efficacy, biocompatibility, and bio-integration. The historically reported immunological privilege of cartilage tissue was based on histomorphological observations pointing out the lack of vascularity and the presence of a tight extracellular matrix. However, clinical studies in humans and animals do not unequivocally support the immune-privilege theory. More in-depth studies on cartilage immunology are needed to make clinical advances such as tissue engineering more applicable. This review analyzes the literature that supports and opposes the concept that cartilage is an immune-privileged tissue and provides insight into mechanisms conferring various degrees of immune privilege to other, more in-depth studied tissues such as testis, eyes, brain, and cancer.

Skulls from 112 Steller sea lions (Eumetopias jubatus) were examined according to predefined criteria. Of the specimens, 73 (65.2%) were from males, 29 (25.9%) from females and 10 (8.9%) were of unknown sex, with 50 adults (44.6%), 61 young adults (54.5%) and one of unknown age (0.9%). The number of teeth evaluated was 3,521. Adults had more acquired tooth loss than young adults (P

The successful excision of a locally invasive tumor such as canine acanthomatous ameloblastoma (CAA) typically results in a mandibular contour-derforming, critical-size defect that alters the jaw kinematics, and may affect the patient's quality of life. In this case series, we describe our experience using the regenerative approach of a titanium locking plate and compression resistant matrix infused with rhBMP-2 for the immediate or delayed reconstruction following mandibulectomy for the excision of mandibular CAA in 11 dogs. Surgical planning included computed tomography (CT), with and without contrast, in all cases, and 3D-printed models in four cases. Tumor-free surgical margins were achieved in all dogs. Clinical and diagnostic imaging follow-up (mean, 23.1 months) were performed in-person (11 cases) and with CT/cone-beam computed tomography in most cases, with standard radiography (3 cases) and telemedicine being utilized in 5 cases. At 2 weeks postoperatively, hard tissue was palpable at the defect. Follow-up imaging at 1 month postoperatively revealed evidence of bridging new bone with a heterogeneous appearance, that remodeled over 3-6 months to bone of a similar size, shape and trabecular pattern as native bone. Histological evaluation of regenerated bone was available in two cases, and was supportive of our clinical and imaging findings of normal remodeled bone. Clinically, all dogs returned to a normal lifestyle, rapidly resumed eating and drinking, and exhibited normal occlusion. Complications included wound dehiscence in one dog and self-limiting exuberant bone formation in two dogs. Tumor regrowth, failure of the implant or fracture of the regenerated bone were not observed. We conclude that the mandibular reconstruction using a regenerative approach is safe, feasible, and results in restoration of mandibular contour in dogs following segmental and bilateral rostral mandibulectomy for benign but invasive oral tumors such as CAA.

ObjectiveTo evaluate the radiographic outcome of root canal treatment (RCT) in dogs and compare outcomes with those reported for a previous study performed at the same institution in 2002.Animals204 dogs representing 281 teeth that underwent RCT.ProceduresThe medical record database of a veterinary teaching hospital was searched to identify dogs that underwent RCT between 2001 and 2018. Only dogs that had undergone at least 1 radiographic recheck appointment a minimum of 50 days after RCT were included in the study. Dental radiographs were reviewed. Treatment was considered successful if the periapical periodontal ligament space was within reference limits and preexisting external inflammatory root resorption (EIRR), if present, had stabilized. Treatment was considered to show no evidence of failure (NEF) if preoperative EIRR had stabilized and any preoperative periapical lucency (PAL) remained the same or had decreased in size but had not completely resolved. Treatment was considered to have failed if EIRR or a PAL developed after RCT, if a preoperative PAL increased in size, or if preexisting EIRR progressed.ResultsFollow-up time ranged from 52 to 3,245 days (mean, 437 days). RCT was classified as successful for 199 (71%) teeth, NEF for 71 (25%) teeth, and failed for 11 (4%) teeth.Conclusions and clinical relevanceResults showed that almost 2 decades after RCT outcome in dogs was first evaluated, during which time numerous advances in dental materials and techniques had been made, the success rate of RCT was virtually unchanged.

The concept of a one-health approach in regenerative medicine has gained tremendous momentum in the scientific and public communities in recent years. Knowledge derived from this approach informs innovative biomedical research, clinical trials, and practice. The ultimate goal is to translate regenerative strategies for curing diseases and improving the quality of life in animals and people. Building and fostering strong and enthusiastic interdisciplinary and transdisciplinary collaboration between teams with a wide range of expertise and backgrounds is the cornerstone to the success of the one-health approach and translational sciences. The veterinarian's role in conducting clinical trials in client-owned animals with naturally occurring diseases is critical and unique as it may potentially inform human clinical trials. The veterinary regenerative medicine and surgery field is on a steep trajectory of discoveries and innovations. This manuscript focuses on oromaxillofacial-region regeneration to exemplify how the concept of interdisciplinary and transdisciplinary collaboration and the one-health approach influenced the authors' work experience at the University of California-Davis.

ObjectiveTo evaluate the biomechanical properties of the mandibles of cats with experimentally created osteotomies simulating oblique ramus fractures, which were stabilized with malleable L-miniplates with either locking screws [locking construct (LC)] or nonlocking screws [nonlocking construct (NLC)], compared with those for intact mandibles.Samples20 mandibles from 10 adult cat cadavers.ProceduresA block study design was adopted to allocate the mandibles of each cadaver to 2 of the 3 test groups (LC, NLC, or intact mandible). Mandibles within each cadaver were allocated systematically to a test group. For mandibles assigned to an LC and an NLC, a complete oblique osteotomy was performed from the mid rostral aspect of the ramus in a caudoventral direction. All mandibles were loaded in a single-load-to-failure test through cantilever bending. Load and actuator displacement were recorded simultaneously. Mode of failure and radiographic evidence of damage to tooth roots and the mandibular canal were evaluated. Biomechanical properties were compared among the groups.ResultsNo iatrogenic tooth root damage was evident, but all mandibles with an LC and an NLC had evidence of screw invasion into the mandibular canal. Plated mandibles had significantly less stiffness and bending moment than intact mandibles. Stiffness was not significantly different between the LC and the NLC; the NLC had a greater bending moment at failure than the LC. The pre-yield stiffness of plated mandibles decreased when the number of screw holes overlapping the mandibular canal increased.Clinical relevanceThe use of a malleable L-miniplate in a caudal mandibular fracture model is feasible. Both the LC and the NLC were inferior mechanically to intact mandibles. Type of construct used did not affect the construct stiffness significantly in tested mandibles.

[This corrects the article DOI: 10.3389/fvets.2020.00241.].

Museum skull specimens represent a non-invasive, informative, and readily available means to study temporomandibular joint (TMJ) lesions, dental pathology, and anatomic variations in many mammalian species. Studying the teeth and jaws of an array of species can present a challenge requiring attention to detail and understanding of a species' normal anatomy. In the present article, a systematic and precise protocol for examining skull specimens is discussed that has been applied to a variety of mammals to define characteristic diseases in the oromaxillofacial region. The procedure outlined is simultaneously precise, repeatable, and adaptable to the highly differing skull and tooth shapes and anatomy across species. Specifically, specimens are examined for missing teeth, periodontal disease, endodontal disease, TMJ pathology, and anatomical variations. Results gleaned from research on museum specimens may reflect the natural history, health, and disease status of individuals and species. Furthermore, these data can inform ecological and conservation research efforts, as well as the care of captive individuals.

Treatment of craniomaxillofacial (CMF) trauma in dogs often requires a multidisciplinary approach and a thorough understanding of the CMF anatomical structures involved. This retrospective study aimed to utilize computed tomography (CT) studies of immature dogs evaluated for CMF trauma and to describe common fracture locations, treatment modalities, and complications, as well as the fracture healing outcomes. The medical records and CT studies of 94 dogs under 1 year of age over a 13-year period were evaluated. The skeletal location of CMF fractures, as well as the severity of displacement and fragmentation of each fracture, was recorded. Case demographic data and trauma etiology were also recorded. Animal bites accounted for the majority of trauma (71.0%). The most likely bone or region to be fractured was the maxillary bones, followed by the molar region of the mandibles. Up to 37 bones or specific regions were fractured in any given patient, with an average of 8.8 ± 3.1 fractured bones or regions per dog. Rostral mandibular trauma was associated with intra-articular fractures of the temporomandibular joint (p = 0.016). Patients sustained concomitant injuries in 32% of the cases. Muzzle therapy was the main treatment performed for most dogs (53.2%), followed by soft tissue closure (47.9%) and selective dental extractions (27.6%). Healing complications were recorded in 71.6% of the dogs, with malocclusion being the most reported complication (55.2%), and associated with dentate mandibular jaw fractures (p = 0.05). The average number of complications per dog was 2.4. No statistically significant association was found between treatment modality and healing outcome. There was a positive correlation between the severity of fracture fragmentation and displacement and a negative healing outcome (all rho >0.7). Further treatment was required in 55.6% of the dogs. Additional dental extractions were performed in 77.7% of patients. Healing complications were common in the immature CMF trauma case. Thus, the need for a comprehensive assessment of the entire CMF region during the initial visit, as well as follow-up, preferably using CT or cone beam CT, is underscored.

Management of complications of fracture fixation in the oromaxillofacial (OMF) region may present a diagnostic and therapeutic challenge. While titanium and stainless steel implants have been utilized in successful fracture fixation in the OMF region, the use of titanium implants is preferred due to the superior intrinsic properties of titanium. Nonetheless, stainless steel materials are still used due to their availability and familiarity. In the present methods report, we describe our approach to the management of failed stainless steel plates and screws used to treat traumatic injuries in the OMF region. Furthermore, we exemplify our approach with five dogs that exhibited complications of stainless steel implants in the OMF region and their subsequent management. In those cases, all failed implants were removed. Reconstruction with a combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) and titanium implants was utilized in two cases while a mandibulectomy was performed in one case. Three cases required removal of the stainless-steel implant with no additional surgical therapy. We conclude that the success of treatment of failed stainless steel implants depends on the use of advanced imaging findings, appropriate antimicrobial therapy, as well as potentially regenerative reconstructive surgery.

Myositis ossificans (MO) and myositis ossificans-like lesions have been rarely described within the veterinary literature, and are even less common in the maxillofacial region. When MO affects the muscles of mastication, it can result in complete or partial inability to open the mouth. As with other conditions resulting in decreased or restricted mandibular range of motion, severe and potentially fatal sequelae such as difficulty with prehension, swallowing, and air exchange are possible. Diagnostic imaging is essential in achieving an accurate diagnosis and in formulating an appropriate treatment plan. In this "method" manuscript, we provide a detailed description of our approach to diagnosis and surgical management of MO-like lesions of the pterygoid muscles and describe our experience with two young French bulldogs.

Multipotent stromal cells (MSCs) are widely utilized in therapy for their immunomodulatory properties, but their usage in infectious viral diseases is less explored. This review aimed to collate the current novel use of MSCs in virus-associated conditions, including MSC's susceptibility to virus infection, antiviral properties of MSCs and their effects on cell-based immune response and implementation of MSC therapy in animal models and human clinical trials of viral diseases. Recent discoveries shed lights on MSC's capability in suppressing viral replication and augmenting clearance through enhancement of antiviral immunity. MSC therapy may maintain a crucial balance between aiding pathogen clearance and suppressing hyperactive immune response.

ObjectivesThe 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.MethodsFive 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.ResultsFour 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 relevanceUnlike 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.

ObjectiveTo 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).Animals19 control cats and 23 cats with FCGS.ProceduresAt 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.ResultsThe 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 relevanceResults 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.

Although the knee joint and temporomandibular joint (TMJ) experience similar incidence of cartilage ailments, the knee orthopedics field has greater funding and more effective end-stage treatment options. Translational research has resulted in the development of tissue-engineered products for knee cartilage repair, but the same is not true for TMJ cartilages. Here, we examine the anatomy and pathology of the joints, compare current treatments and products for cartilage afflictions, and explore ways to accelerate the TMJ field. We examine disparities, such as a 6-fold higher article count and 2,000-fold higher total joint replacement frequency in the knee compared to the TMJ, despite similarities in osteoarthritis incidence. Using knee orthopedics as a template, basic and translational research will drive the development and implementation of clinical products for the TMJ. With more funding opportunities, training programs, and federal guidance, millions of people afflicted with TMJ disorders could benefit from novel, life-changing therapeutics.

Septic arthritis of the temporomandibular joint (TMJ) in dogs and other mammals is a rare condition. It is typically associated with notable pain, swelling, and difficulty in opening the mouth. Unlike degenerative TMJ disease, septic arthritis requires urgent intervention. The etiology of the condition may include penetrating trauma, an extension of local infection, such as otitis media, or the hematogenous spread of a pathogen. However, the precise cause may not always be identified. Diagnostic imaging with Computed Tomography (CT), cone-beam CT (CBCT), and/or Magnetic Resonance Imaging (MRI) are helpful for honing the definitive diagnosis and formulating a treatment plan. Subsequently, exploratory surgery may be required to obtain samples for culture and sensitivity and histology and to lavage the joint. In this "methods" article, we provide a detailed description of our approach to diagnosis and management of septic TMJ arthritis in four dogs.

Degenerative changes of the temporomandibular joint (DTMJ) may be diagnosed via cone - beam computed tomography (CBCT). However, despite advancement in CBCT imaging, correlation of DTMJ features identified on CBCT with gross and histological findings is currently limited. This study aimed to correlate CBCT findings of DTMJ of dogs with gross and histopathologic changes. Temporomandibular joints (TMJ) (n = 38) from fresh cadaver heads of asymptomatic dogs (n = 19) were examined radiologically, macroscopically, and microscopically. Association of CBCT - detected DTMJ changes with gross and histological findings were statistically evaluated via kappa statistics and ordinal logistic mixed-effects models. The radiological changes observed on CBCT included joint space narrowing, subchondral/cortical bone changes (i.e., erosions or lysis), osteophytes, and subchondral bone sclerosis. Upon macroscopic evaluation, the majority of examined specimens had mild changes with cartilage defects and osteophytes affecting

Approximately 9 out of 10 adults have some form of periodontal disease, an infection-induced inflammatory disease of the tooth-supporting tissues. The initial form, gingivitis, often remains asymptomatic, but this can evolve into periodontitis, which is typically associated with halitosis, oral pain or discomfort, and tooth loss. Furthermore, periodontitis may contribute to systemic disorders like cardiovascular disease and type 2 diabetes mellitus. Control options remain nonspecific, time-consuming, and costly; largely relying on the removal of dental plaque and calculus by mechanical debridement. However, while dental plaque bacteria trigger periodontal disease, it is the host-specific inflammatory response that acts as main driver of tissue destruction and disease progression. Therefore, periodontal disease control should aim to alter the host's inflammatory response as well as to reduce the bacterial triggers. Vaccines may provide a potent adjunct to mechanical debridement for periodontal disease prevention and treatment. However, the immunopathogenic complexity and polymicrobial aspect of PD appear to complicate the development of periodontal vaccines. Moreover, a successful periodontal vaccine should induce protective immunity in the oral cavity, which proves difficult with traditional vaccination methods. Recent advances in mucosal vaccination may bridge the gap in periodontal vaccine development. In this review, we offer a comprehensive overview of mucosal vaccination strategies to induce protective immunity in the oral cavity for periodontal disease control. Furthermore, we highlight the need for additional research with appropriate and clinically relevant animal models. Finally, we discuss several opportunities in periodontal vaccine development such as multivalency, vaccine formulations, and delivery systems.

In the past decade, the potential to translate scientific discoveries in the area of regenerative therapeutics in veterinary species to novel, effective human therapies has gained interest from the scientific and public domains. Translational research using a One Health approach provides a fundamental link between basic biomedical research and medical clinical practice, with the goal of developing strategies for curing or preventing disease and ameliorating pain and suffering in companion animals and humans alike. Veterinary clinical trials in client-owned companion animals affected with naturally occurring, spontaneous disease can inform human clinical trials and significantly improve their outcomes. Innovative cell therapies are an area of rapid development that can benefit from non-traditional and clinically relevant animal models of disease. This manuscript outlines cell types and therapeutic applications that are currently being investigated in companion animals that are affected by naturally occurring diseases. We further discuss how such investigations impact translational efforts into the human medical field, including a critical evaluation of their benefits and shortcomings. Here, leaders in the field of veterinary regenerative medicine argue that experience gained through the use of cell therapies in companion animals with naturally occurring diseases represent a unique and under-utilized resource that could serve as a critical bridge between laboratory/preclinical models and successful human clinical trials through a One-Health approach.

BackgroundThe ability of mesenchymal stem cells (MSCs) to modulate immune responses inspired a series of clinical trials addressing oral mucosal inflammation. We previously reported on the safety and efficacy of fresh, allogeneic and autologous, adipose-derived mesenchymal stem cells (ASCs) to treat feline gingivostomatitis (FCGS), an oral mucosal inflammatory disease that shares similarities with human oral lichen planus.MethodsTo meet clinical demand and goals for future commercialization, we determined the feasibility of shipping fresh ASCs to distant clinics and extended our pilot studies to expand safety and efficacy data for shipped and non-shipped ASCs in a cohort of 18 FCGS cats enrolled locally and at a few different locations within the USA.ResultsWe found that ASCs retained their viability, phenotype, and function after shipment. ASCs administered systemically resulted in a 72% positive response rate, identical to that noted in our previous studies. Cats that responded to ASC therapy had a significant decrease in circulating globulin concentration and histological evidence of decreased CD3+ T cells and CD20+ B cells in the oral mucosa. Responder cats also had significantly decreased percentages of CD8lo cells in blood prior to and at 3 months post-ASC therapy. CD8lo cells may serve as a potential "predictor" for response to systemic ASC therapy.ConclusionFresh feline ASCs can be successfully shipped and administered to cats with FCGS. ASCs modulate the immune response and demonstrate efficacy for chronic oral mucosal inflammatory lesions that are characterized by CD8+ T cell inflammation and T cell activation. FCGS is a potentially useful naturally occurring large animal model of human oral inflammatory diseases.

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.

Feline chronic gingivostomatitis (FCGS) is an immune-mediated inflammatory condition affecting the oral mucosa that results in substantial pain and suffering. The goal of this study was to complete an in-depth immunohistochemistry analysis of affected FCGS mucosa, to perform and compare immune cell phenotypes in the blood of FCGS and healthy controls cats, and to determine a transcriptomic profile of the affected and normal oral mucosa of FCGS cats. We hypothesized that cats with FCGS would have circulating activated CD8+ T cells and that tissues would be infiltrated with activated B and T cells with a highly proinflammatory transcriptome. We found that oral mucosal tissues from cats with FCGS have high tissue infiltration of B cells and that T cells include both CD4+ and CD8+ lymphocytes. Cells positive for CD25 (IL2 receptor, indicative of lymphocyte activation) and FOXP3 (indicative of regulatory T cells) were scattered throughout the mucosa. Compared to healthy individuals, cats with FCGS had high circulating CD8+ effector memory cells with a concurrent decrease in central memory cells and evidence of circulating activated CD8+ T cells (CD25+, CD62L-). Gene expression in the affected tissues was enriched for genes associated with T-cell signaling, cell adhesion molecules, leukocyte migration, inflammatory signaling pathways, extracellular matrix-receptor interactions, cytokine-cytokine receptor interactions, and natural killer cell-mediated cytotoxicity, among others. These data are essential to understand disease pathogenesis, to inform mechanism of action studies for future and current therapies, and to help select prognostic biomarkers and potency assays for stem cell treatment of FCGS.

Temporomandibular joint (TMJ) ankylosis is defined as fibrous or bony fusion of the mandibular head of the condylar process and the mandibular fossa of the squamous part of the temporal bone. Ankylosis of the TMJ may be intraarticular, extraarticular, or both. The objective of this report is to describe the surgical planning, technique, and outcome of gap arthroplasty for extensive TMJ ankylosis in cats. Client-owned cats (n = 7) were examined clinically and surgical planning included the use of cone-beam computed tomography (CBCT) and tridimensional (3D) printed models. In six of the seven cats, temporary tracheostomy intubation was required. Gap arthroplasty included zygomectomy, coronoidectomy, condylectomy, as well as fossectomy (removal of the mandibular fossa of the temporal bone) and was performed using a piezosurgical unit. In all seven cats, gap arthroplasty was performed without surgical complications. In addition, a clinically acceptable mouth opening was achieved in all cases. However, a noticeable mandibular instability was observed. Medium-term follow-up demonstrated acceptable quality of life with one case of recurrence of ankylosis requiring repeated bilateral surgery, and a second case with recurrence of ankylosis not requiring surgical intervention at the time of manuscript preparation. We concluded that TMJ gap arthroplasty in cats is a salvage procedure indicated in cases of severe intraarticular and extraarticular ankylosis. Diagnostic imaging by means of CBCT and 3D printing are essential for precise surgical planning. The use of a piezosurgical unit allows for safe and precise ostectomy. Clinically, despite the resulting mandibular instability, appropriate prehension of food and water was possible.