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Mesenchymal stem cells (MSCs) appear to be safe for cellular therapy across allogeneic barrier. MSCs have the potential for tissue regeneration of mesodermally-derived cells, such as bone, cartilage, and adipose, and also cells of ectodermal origin. The immune properties of MSCs are relevant to their potential application for hyper immune diseases such as the treatment of autoimmune and other inflammatory disorders. MSCs exert immune suppressor functions such as decrease in T-cell proliferation and effector cell function, with concomitant expansion of regulatory T cells. In light of dampened outcome from recent clinical trials with MSCs, this chapter discusses how the immune microenvironment and local cytokine milieu can dictate the effects of MSCs on various biological processes. For example, variations in the local concentration of interferon-γ (IFN-γ) can influence the antigen-presenting function of MSCs, thereby making MSCs immune suppressor or enhancer. The diverse effects of MSCs as well as the potential confounds by an inflamed microenvironment are highlighted to emphasize the need to understand the basic biology of MSCs for effective treatment for tissue repair or resetting the immune system.

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