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.

Thrombelastograph analyzers are point-of-care hemostatic analyzers that provide global assessment of the hemostatic process. Thrombelastography (TEG) detects and provides a continuous recording of the changes in the viscoelastic properties of whole blood from initial clot formation through fibinolysis. TEG has been validated for use in dogs, horses, and cats. Hemostasis research using TEG has focused on test validation, alterations of TEG tracings in animals with naturally occurring diseases, and the use of TEG for monitoring various therapeutic modalities. This article reviews TEG methodology and terminology, including potential sources of preanalytical and analytical errors, the correlation between TEG and other routine hemostatic assays, and current clinical applications of TEG, with emphasis on veterinary medical practice. Data suggest that TEG may be a sensitive and useful adjunctive tool for evaluating an animal with an underlying coagulopathy, including hypercoagulability and hypocoagulability. Additional prospective studies are needed to (1) correlate TEG tracing patterns with a clinical predisposition for bleeding or thrombosis in various disease states and (2) determine whether monitoring and treating hemostatic disorders based on TEG tracings improve clinical outcome.

Mesenchymal stem cells (MSCs) are somatic, multipotent stromal cells with potent immunomodulatory and regenerative properties. Although MSCs have pattern recognition receptors and are modulated by Toll-like receptor ligands, MSC-microbial interactions are poorly defined. The objectives of this study were to determine the effect of bacterial association on MSC function. We hypothesized that gastrointestinal bacteria associate with MSCs and alter their immunomodulatory properties. The effect of MSC-microbial interactions on MSC morphology, viability, proliferation, migration, and immunomodulatory functions was investigated. MSCs associated with a remarkable array of enteric pathogens and commensal bacteria. MSC interactions with two model organisms, the pathogen Salmonella typhimurium and the probiotic Lactobacillus acidophilus, were further investigated. While ST readily invaded MSCs, LB adhered to the MSC plasma membrane. Neither microbe induced MSC death, degeneration, or diminished proliferation. Microbial association did not upregulate MHC-II, CD80/86, or CD1 expression. MSCmicrobial interaction significantly increased transcription of key immunomodulatory genes, including COX2, IL6, and IL8, coupled with significantly increased prostaglandin E 2 (PGE 2 ), interleukin (IL)6, and IL8 secretion. MSC-ST coincubation resulted in increased MSC expression of CD54, and significant augmentation of MSC inhibition of mitogen-induced T-cell proliferation. T-cell proliferation was partially restored when PGE 2 secretion was blocked from ST-primed MSCs. MSC-microbe interactions have a profound effect on MSC function and may be pivotal in a variety of clinical settings where MSCs are being explored as potential therapeutics in the context of microbial communities, such as Crohn's disease, chronic nonhealing wounds, and sepsis.

Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs) injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM) or adipose tissue derived MSCs (ad-MSCs) were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89%) were positive for anti-bovine serum albumin (BSA) antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.