Introduction: Autologous mesenchymal stem cells (MSCs) are an attractive concept in regenerative medicine, but\ntheir mechanism of action remains poorly defined. No immune response is reported after in vivo injection of\nallogeneic equine MSCs or embryo-derived stem cells (ESCs) into the equine tendon, which may be due to the\ncells� immune-privileged properties. This study further investigates these properties to determine their potential for\nclinical application in other tissues.\nMethods: Mitomycin C-treated MSCs, ESCs, or differentiated ESCs (dESCs) were cultured with allogeneic equine\nperipheral blood mononuclear cells (PBMCs), and their effect on PBMC proliferation, in the presence or absence of\ninterferon-gamma (IFN-?) was determined. MSCs and super-antigen (sAg)-stimulated PBMCs were co-cultured\ndirectly or indirectly in transwells, and PBMC proliferation examined. Media from MSC culture were harvested and\nused for PBMC culture; subsequent PBMC proliferation and gene expression were evaluated and media assayed for\nIFN-?, tumor necrosis factor alpha (TNF-?), and interleukin (IL)-10 and IL-6 proteins with enzyme-linked immunosorbent\nassay (ELISA).\nResults: Co-culture of PBMCs with ESCs or dESCs did not affect baseline proliferation, whereas co-culture with\nMSCs significantly suppressed baseline proliferation. Stimulation of PBMC proliferation by using super-antigens\n(sAgs) was also suppressed by co-culture with MSCs. Inhibition was greatest with direct contact, but significant\ninhibition was produced in transwell culture and by using MSC-conditioned media, suggesting that soluble factors\nplay a role in MSC-mediated immune suppression. The MSCs constitutively secrete IL-6, even in the absence of\nco-culture with PBMCs. MSC-conditioned media also brought about a change in the cytokine-expression profile of\nsAg-stimulated PBMCs, significantly reducing PBMC expression of IL-6, IFN-?, and TNF-?.\nConclusions: Equine MSCs and ESCs possess a degree of innate immune privilege, and MSCs secrete soluble\nfactors that suppress PBMC proliferation and alter cytokine expression. These properties may make possible\nthe future clinical use of allogeneic stem cells to help standardize and broaden the scope of treatment of\ntissue injuries.
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