Donor-specific Mesenchymal Stem Cell Infusion in Human and Non-human Primate Kidney Transplantation.

We report the results of two independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell (MSC) infusions in inducing immune-tolerance in nonhuman primate (NHP) and human kidney transplant recipients treated with depletional induction and belatacept/sirolimus maintenance. Fifteen NHPs received rhesus ATG induction and were divided in three groups: control (n=6), pre-transplant thymic irradiation (TI, n=4), and TI with monthly donor-MSC infusion (n=5). Sirolimus was discontinued at day-180, and belatacept at day-365 post-transplantation. In humans, six patients enrolled in ITN062ST underwent transplantation with alemtuzumab induction; four received 12 monthly donor-MSC infusions followed by immunosuppression withdrawal (ISW) if eligible. Donor-MSC infusion was acutely well-tolerated in humans and NHPs. Chimerism was not established, and tolerance was not induced in either study. Two of five NHPs that received MSCs rejected while on belatacept monotherapy with detectable donor-specific antibody (DSA). Two patients did not initiate ISW due to de novo DSA and borderline rejection, and two patients failed ISW due to reversible rejection. In conclusion, donor-MSCs can be given to NHPs or humans repeatedly without acute consequences, but they neither lead to detectable chimerism nor induce tolerance. In a subset of recipients, infused MSCs can be sensitizing. Trial Registration. ClinicalTrials.gov - NCT03504241.