Evaluation of Immunomodulatory Properties of Feline Mesenchymal Stem Cells.

ABSTRACT

Mesenchymal stem cells (MSC) offer a novel approach to treatment of inflammatory disorders in humans and companion animals. Cats spontaneously develop a wide variety of inflammatory disorders and may potentially benefit from MSC-based therapies. Multiple genes are involved in immunomodulation by MSC and interspecies differences between expressions of these genes exist. The goals of the study were to characterize the expression of genes known to be involved in MSC-based immunomodulation and determine the effect of MSC on proliferation of T cells in coculture experiments with peripheral blood mononuclear cells (PBMC). Unstimulated MSC expressed all immunomodulatory genes studied except for IL-10. Levels of iNOS and FASL were low or undetectable at the RNA level. INFγ stimulation resulted in significant dose-dependent upregulation of IDO1, PD-L1, IL-6, COX2, and HGF. Levels of kynurenine were increased after 3-day incubation with INFγ. TNFα stimulation increased expression of IL-6 at both RNA and protein level as well as upregulated COX2 gene expression and PTGES1.Stimulation with both INFγ and TNFα resulted in significant increase in PGE2 levels in cell culture medium. MSC significantly decreased proliferation of ConA-stimulated PBMC in coculture experiments at 15 ratio. Our results suggest that feline MSC have similar immunomodulatory gene expression and react to inflammatory cytokines in a manner similar to human MSC. Thus, MSC may play an important role in treatment of feline disease as well as serve as an important translational species to evaluate MSC-based therapies of diseases common to both humans and cats.