Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into mesenchymal lineages and that can be isolated from various tissues and easily cultivated in vitro. Currently, MSCs are of considerable interest because of the biological characteristics that confer high potential applicability in the clinical treatment of many diseases. Specifically, because of their high immunoregulatory capacity, MSCs are used as tools in cellular therapies for clinical protocols involving immune system alterations. In this review, we discuss the current knowledge about the capacity of MSCs for the immunoregulation of immunocompetent cells and emphasize the effects of MSCs on T cells, principal effectors of the immune response, and the immunosuppressive effects mediated by the secretion of soluble factors and membrane molecules. We also describe the mechanisms of MSC immunoregulatory modulation and the participation of MSCs as immune response regulators in several autoimmune diseases, and we emphasize the clinical application in graft versus host disease (GVHD).

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BackgroundIn recent years, immunomodulatory mechanisms of mesenchymal stem/stromal cells (MSCs) from bone marrow and other “classic” sources have been described. However, the phenotypic and functional properties of tumor MSCs are poorly understood. The aim of this study was to analyze the immunosuppressive capacity of cervical cancer-derived MSCs (CeCa-MSCs) on effector T lymphocytes through the purinergic pathway.MethodsWe determined the expression and functional activity of the membrane-associated ectonucleotidases CD39 and CD73 on CeCa-MSCs and normal cervical tissue-derived MSCs (NCx-MSCs). We also analyzed their immunosuppressive capacity to decrease proliferation, activation and effector cytotoxic T (CD8+) lymphocyte function through the generation of adenosine (Ado).ResultsWe detected that CeCa-MSCs express higher levels of CD39 and CD73 ectonucleotidases in cell membranes compared to NCx-MSCs, and that this feature was associated with the ability to strongly suppress the proliferation, activation and effector functions of cytotoxic T-cells through the generation of large amounts of Ado from the hydrolysis of ATP, ADP and AMP nucleotides.ConclusionsThis study suggests that CeCa-MSCs play an important role in the suppression of the anti-tumor immune response in CeCa through the purinergic pathway.

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Psoriasis is a skin disease characterized by hyperproliferation of keratinocytes and chronic inflammation. Mesenchymal stem/stromal cells (MSCs) exhibit an immunoregulatory function that can be altered in the skin of these patients. However, to date, the presence and functional capacity of MSCs in the dermis and epidermis of patients with psoriasis have not been fully established. In the present study, we evaluated the presence of MSCs in the skin of patients by obtaining adherent cells from the dermis and epidermis of lesional and nonlesional areas and characterizing them in a comparative manner with corresponding cells obtained from the dermis (HD-MSCs) and epidermis (HE-MSCs) of healthy donors. We determined whether the adherent cells had immunophenotypic profiles and differentiation potentials that were characteristic of MSCs. In addition, we analyzed their immunosuppression function by evaluating their capacity to decrease T cell proliferation. Our results indicate the presence of MSCs in the dermis and epidermis of healthy donors and patients with psoriasis; adherent cells from all skin sources exhibited MSC characteristics, such as expression of CD73, CD90, and CD105 markers and a lack of hematopoietic and endothelial marker expression. However, the cell populations obtained showed differences in differentiation potential toward adipogenic, osteogenic, and chondrogenic lineages. In addition, we observed a low MSC obtention frequency in nonlesional epidermal samples (NLE-MSCs), which also showed alterations in morphology and proliferation rate. Interestingly, MSCs from both the nonlesional dermis (NLD-MSCs) and lesional dermis (LD-MSCs) showed higher HLA class I antigen (HLA-I) expression than HD-MSCs. Moreover, NLD-MSCs showed a low T cell proliferation suppression capacity. In summary, this study demonstrates the presence of MSCs in the epidermis and dermis of patients with psoriasis and suggests that such cells may favor the inflammatory process and thus psoriatic lesion development through high HLA-I expression and low immunosuppression capacity.