Human bone marrow stem cells, more recently referred to as MSCs, are multipotential cells that reside within the bone marrow and can differentiate into various components of the marrow microenvironment, in addition to supporting growth of hematopoietic progenitors.There is also evidence that MSCs escape the immune system, and therefore could be infused into an allogeneic host without being rejected and without requirement of conditioning regimens. Moreover, they exert an immunoregulatory activity, although the exact mechanism of action is unknown. On this line, evidence is available that MSC inhibit naïve T cells and lock dendritic cells (DC) into a semi-mature state, thereby favoring peripheral tolerance. It should be also pointed out that experimental in vitro evidence has shown that mouse MSCs inhibit the response of memory antigen-specific T cells to their cognate peptide. We expect that, in kidney transplant recipients, MSC infusion would allow inhibition of alloantigen-specific memory T cell response contributing to long-term graft survival. Moreover in vitro studies have documented that the CD4+CD25+ T regulatory cell population increased significantly in MLR when human MSCs were present compared to controls without MSCs. These findings suggest that MSC may modulate T cell response even through a regulatory mechanism. Furthermore an immunosuppressive effect of MSCs in vivo has been shown in a baboon model, in which infusion of ex-vivo expanded matched donor or third-party MSCs delayed the time to rejection of histoincompatible skin graft. The immunomodulatory function of MSCs has been also documented in preliminary in vivo studies in humans, where cell infusion did exert preventive effects on the development of acute and chronic GVHD. Thus, although no data so far are available in human kidney transplantation, we expect that peri-transplant intravenous infusion of syngeneic ex-vivo expanded MSCs under peripheral T-cell depletion/blockade with basiliximab and low dose RATG (as induction therapy) and the cover of low dose maintenance immunosuppressive drugs would allow to safety achieving graft tolerance in living-related kidney transplant recipients. This could be through inhibition of both naïve and memory T cells, and promotion of development and activation of regulatory T cells, eventually leading to indefinite graft survival.