Kidney transplant tolerance associated with remote autologous mesenchymal stromal cell administration.

Federica Casiraghi,Eliana Gotti,Monica Cortinovis,Alessandro Villa,Valentina Portalupi,Marilena Mister,Giuseppe Remuzzi,Marta Todeschini,Norberto Perico,Martino Introna,Anna Rita Plati,Elena Longhi,Flavio Gaspari

doi:10.1002/sctm.19-0185

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.

Highlights

This patient was successfully weaned off immunosuppressive drugs and is 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. This case report provides the first evidence that in livingdonor kidney transplantation autologous bone marrowderived 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
We present results from the first reported case of a MSC-treated kidney transplant patient successfully weaned off immunosuppressive drug therapy and describe changes in the host immune microenvironment following cell treatment, a potential mechanism of action through which the modulation of immune regulatory pathways may impact graft rejection and enable the development and retention of a state of donor-specific graft tolerance
We are confident that the donor-specific immune tolerance achieved by our patient is not the result of particular pretransplant characteristics of the recipient, donor, or graft quality, but just the effect of the pro-tolerogenic environment promoted by MSC infusion. This is supported by previous findings we reported in a control group of kidney transplant patients of comparable mean age at transplantation, similar causes of renal failure, as well as median human leukocyte antigen (HLA) mismatch with the donor, and donor age, who received induction therapy with low-dose thymoglobulin alone or in combination with basiliximab, but not MSC.[15]