Our findings provide evidences supporting involvement of HLA-G in the immunosuppressive properties of MSCs. These results emphasize the potential application of MSCs as a relevant therapeutic candidate in transplantation.

Mesenchymal stem cells (MSC) inhibit the response of allogeneic T lymphocytes in culture. Because the mechanisms of this effect may differ according to the existence of cell contact, we investigated the differences in gene expression of inhibitory molecules during MSC-T lymphocyte coculture when cell contact does and does not occur. Human MSC and T lymphocytes were cultured together in standard and transwell cultures. MSC gene expression was analyzed by semiquantitative real-time RT-PCR. MSC elicited a high dose-dependent inhibition of T lymphocytes in cultures with cell contact, but inhibition occurred even without cell contact. In both cases, we observed significant upregulation of IDO, LIF, and HLA-G, along with downregulation of HGF and SDF1. In cultures with cell contact, IL-10 and TGF-β transcripts were expressed in a significantly higher level than in cultures without this contact. Furthermore, in the latter, the increased inhibition of T-cell proliferation was positively correlated with IDO gene expression and negatively correlated with SDF1 gene expression. MSC appear to induce T-cell tolerance by two distinct mechanisms. The first of these, which does not require cell contact, induces expression of the tolerogenic genes IDO, LIF, and HLA-G. The second mechanism, which is contact dependent, modulates IL-10 and TGF-β gene expression. These two mechanisms probably play separate roles in MSC-induced tolerance in allogeneic hematopoietic stem cell transplantation.

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Co-transplantation of mesenchymal stem cells (MSCs) and hematopoietic stem cells ameliorate hematopoietic reconstitution and induce tolerance. The immunomodulatory properties of MSCs have been demonstrated both in vivo and in vitro. MSCs can modulate function of immune cells such as T lymphocytes, antigen-presenting cells and natural killer cells. However, it is unknown whether MSCs given to patients that have undergone HSC transplantation could alleviate graft versus leukemia effect or could increase the risk of the infection. Proper characterization of MSC immunomodulatory mechanisms are crucial to anticipate the possible effect of MSC in the host. In the current report, interesting and contradictory results in the literature are reviewed in an attempt to understand the underlying mechanism. Differences in experimental designs and models used seem to be the underlying causes of discrepancy in reported results. Results of the few in vivo studies are controversial and further clinical studies are needed to confirm the efficiency and safety of MSCs in transplantation management.