ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2025
Donor-specific mesenchymal stem cell infusion in human and nonhuman primate kidney transplantation.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
We report the results of 2 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 into 3 groups: control (n = 6), pretransplant thymic irradiation (n = 4), and thymic irradiation with monthly donor-MSC infusion (n = 5). Sirolimus was discontinued at day-180, and belatacept at day-365 posttransplant. In humans, 6 patients enrolled in ITN062ST underwent transplantation with alemtuzumab induction; 4 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 the 5 NHPs that received MSCs rejected while on belatacept monotherapy with detectable donor-specific antibodies. Two patients did not initiate ISW due to de novo donor-specific antibodies and borderline rejection, and 2 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.
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