The use of fresh, autologous, adipose-derived mesenchymal stem cells (ASCs) was studied for treatment of feline chronic gingivostomatitis. Cats received autologous ASCs, and immunomodulatory effects were assessed. The five cats that responded to treatment also exhibited systemic immunomodulation. Response to ASC therapy was seen only in cats with <15% CD8lo cells, suggesting relative absence of CD8lo cells may be a biomarker of treatment response.

Knowledge and resources derived from veterinary medicine represent an underused resource that could serve as a bridge between data obtained from diseases models in laboratory animals and human clinical trials. Naturally occurring disease in companion animals that display the defining attributes of similar, if not identical, diseases in humans hold promise for providing predictive proof of concept in the evaluation of new therapeutics and devices. Here we outline comparative aspects of naturally occurring diseases in companion animals and discuss their current uses in translational medicine, benefits, and shortcomings. Last, we envision how these natural models of disease might ultimately decrease the failure rate in human clinical trials and accelerate the delivery of effective treatments to the human clinical market.

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 are 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 pain.

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 CD8lo 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

Treatments for temporomandibular joint (TMJ) disc thinning and perforation, conditions prevalent in TMJ pathologies, are palliative but not reparative. To address this, scaffold-free tissue-engineered implants were created using allogeneic, passaged costal chondrocytes. A combination of compressive and bioactive stimulation regimens produced implants with mechanical properties akin to those of the native disc. Efficacy in repairing disc thinning was examined in minipigs. Compared to empty controls, treatment with tissue-engineered implants restored disc integrity by inducing 4.4 times more complete defect closure, formed 3.4-fold stiffer repair tissue, and promoted 3.2-fold stiffer intralaminar fusion. The osteoarthritis score (indicative of degenerative changes) of the untreated group was 3.0-fold of the implant-treated group. This tissue engineering strategy paves the way for developing tissue-engineered implants as clinical treatments for TMJ disc thinning.

Developing a platform for in vitro cartilage formation would enhance the study of cartilage development, pathogenesis, and regeneration. To improve neocartilage formation, our group developed a novel self-assembly process for articular chondrocytes, which has been improved in this study using a novel combination of catabolic and anabolic agents. TGF-β1 was applied in conjunction with the enzyme chondroitinase-ABC (C-ABC) to additively increase tensile properties and synergistically enhance collagen content. Additionally, microarray analysis indicated that TGF-β1 up-regulated MAPK signaling in contrast to C-ABC, which did not enrich genetic pathways. The lack of genetic signaling spurred investigation of the biophysical role of C-ABC, which showed that C-ABC treatment increased collagen fibril diameter and density. After four weeks of culture in nude mice, neocartilage exhibited stability and maturation. This study illustrated an innovative strategy for improving in vitro and in vivo articular cartilage formation and elucidated mechanisms underlying TGF-β1 and C-ABC treatment.

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 5 28) and cats (n 5 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 5 12 dogs) or defect nonunion fracture (n 5 6 dogs, 2 cats), mapping of ostectomy location for temporomandibular joint ankylosis or pseudoankylosis (n 5 4 dogs), assessment of palatal defects (n 5 2 dogs, 1 cat), improved understanding of complex anatomy in cases of neoplasia located in challenging locations (n 5 2 dogs, 1 cat), and in cases of altered anatomy secondary to trauma (n 5 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.

Incisor tooth resorption, in particular external replacement resorption and external inflammatory resorption, is common in horses. Hypercementosis is consistently associated with resorption, but the inverse association is inconsistent.