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Friday Science Review: January 6, 2012

MSC Anti-Immune Power

McGill University ♦ Published in Molecular Therapy (npg), January 2012

Mesenchymal stem cells have great potential as a source of therapeutic cell types for transplantation because they are capable of differentiating into bone, fat, cartilage, and muscle. Some reports show they even have the ability to differentiate into neural cells. The research community is beginning to learn, however, that perhaps the most interesting application of MSCs will be as a suppressant for the immune system. MSCs exhibit the unique ability to moderate T cell response. As a result, they are being investigated in clinical studies for treatment of disorders characterized by inflammation and autoimmunity. Rheumatoid arthritis is a model indication for MSC therapy down the line.

Results from clinical trials thus far have been varied. In order to gain a mechanistic understanding of the variability clinicians are observing, researchers at McGill University cross-examined MSCs from normal adult volunteers. Using an in vitro model, 7 different MSC lines were tested for their ability to suppress T cell proliferation. Results of this study indicate that MSCs possessing the most potent anti-immune power upregulate expression of an enzyme known as indoleamine 2,3-dioxygenase (IDO) in response to interferon-α. IDO is the first enzyme in the kynurenine pathway that catalyzes the degradation of trytophan. Several of the metabolites of this pathway are known to activate the stress response kinase CGN2, which causes apoptosis of T cells. Researchers also found that IDO activity is implicated in the differentiation of monocytes into immunosuppressive macrophages that regulate T cell proliferation in an IL-10 dependent fashion.

Elucidating the molecular mechanisms that contribute to the ability of MSCs to temper the immune system will allow us to generate MSC lines that have the most potent anti-immune power for the treatment of inflammatory and autoimmune disease.

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