Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow Stem Cells

Comparison of gene expression profiles of canine adipose and bone marrow derived mesenchymal stem cells by microarray Mesenchymal stem cells (MSC) from rodents and humans have been shown to suppress T cells by distinct primary pathways, with NO-dependent pathways dominating in rodents and IDO-dependent pathways dominating in humans. However, the immune suppressive pathways utilized by canine MSC have not been as thoroughly studied, nor have BM-MSC and Ad-MSC been directly compared for their immune modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC were generated in vitro and their potency in suppressing T cell proliferation and cytokine production was compared, as well as differential gene expression. Mechanisms of T cells suppression were also investigated for both MSC types. We found that BM-MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T cell activation. However, the two MSC types used both shared and distinct biochemical pathways to suppress T cell activation. Adipose-derived MSC utilized, TGF-β signaling pathways and adenosine signaling to suppress T cell activation, whereas BM-MSC used cyclooxygenase TGF-β, and adenosine signaling pathways to suppress T cell activation. These results indicate that canine MSC are distinct from human and rodent MSC terms of their immune suppressive pathways, relying primarily on cyclooxygenase and TGF-β pathways for T cell suppression, rather than on NO or IDO-mediated pathways. Mesenchymal stem cells were derived from extracted canine adipose and bone marrow, cells were passaged in vitro and RNA extracted at low passages for analysis on Affymetrix microarray