Based on their ability to regulate immune responses, MSCs are considered to be potential candidates for managing immune-mediated diseases in the context of immune therapy. AT and WJ are considered valuable alternatives for BM as a source of MSCs. A detailed and comparative characterization of the immunological profile of MSCs derived from different sources, as well as an understanding of their responsiveness under certain circumstances, such as inflammation, is required to facilitate efficient and well-designed clinical studies. Flow cytometric analyses revealed clear differences among MSC types concerning the expression of the endothelial (e.g., CD31, CD34, CD144 and CD309) and stromal (e.g., CD90 and CD105) associated markers. Regardless of their source, MSCs did not express any of the known hematopoietic markers. All MSCs were uniformly positive for HLA-ABC and lacked the expression of HLA-DR and the co-stimulatory molecules (e.g., CD40, CD80, CD86, CD134 and CD252) required for full T-cell activation. Tissue-specific MSCs presented a modulated expression of cell adhesion molecules that is important for their cellular interactions. MSCs exhibited several surface (e.g., CD73, HLA-G, HO-1 and CD274) and soluble (e.g., HGF, PGE2 and IGFBP-3) immunoregulatory molecules. According to these immunological profiles, the present work provides evidence that the source from which MSCs are derived is important for the design of MSC-based immunointervention approaches. In light of these observations, we may suggest that WJ-MSCs appear to be the most attractive cell population to use in immune cellular therapy when immunosuppressive action is required.