Kidney transplant tolerance associated with remote autologous mesenchymal stromal cell administration

Abstract

Abstract Here we report the case of successful immune tolerance induction in a living-donor kidney transplant recipient remotely treated with autologous bone marrow-derived mesenchymal stromal cells (MSC). This case report, which to the best of our knowledge is the first in the world in this setting, provides evidence that the modulation of the host immune system with MSC can enable the safe withdrawal of maintenance immunosuppressive drugs while preserving optimal long-term kidney allograft function. Lessons learned Autologous bone marrow-derived mesenchymal stromal cells (MSCs) infusion in kidney transplant recipients promoted a sustained and long-lasting pro-tolerogenic immune environment. This immune profile was particularly remarkable in a kidney transplant patient. This patient was successfully weaned off immunosuppressive drugs and is now 18 months free from antirejection therapy with optimal kidney allograft function. This case report provides evidence that MSC could modulate the host immune system, enabling the induction of operational tolerance, and sets the basis for future clinical trials in solid organ transplantation.  Significance statementThis case report provides the first evidence that in living-donor kidney transplantation autologous bone marrow-derived mesenchymal stromal cells (MSCs) infusion can be associated with safe, complete discontinuation of maintenance antirejection drugs late after transplant, eventually allowing a state of operational tolerance. This case could be also preparatory for future studies to assess whether a panel of noninvasive immunomonitoring tools, in addition to clinical criteria, could identify a pro-tolerogenic signature after MSC therapy that could eventually help to identify patients who are amenable to safe immunosuppressive drug discontinuation. Further investigations building on this approach are critically needed in living-donor as well as in deceased donor kidney transplantation.