Longevity & AgingDonor Stem Cell Infusions Fail to Induce Kidney Transplant Tolerance and May Sensitize
Two concurrent studies—one in rhesus macaques, one in six human kidney transplant recipients—tested whether monthly infusions of donor-derived mesenchymal stromal cells (MSCs) could promote immune tolerance and allow immunosuppression withdrawal. All participants received depletional induction plus belatacept and sirolimus maintenance. MSC infusions were acutely well-tolerated in both species. However, donor chimerism was never detected, and operational tolerance was never achieved. In a troubling subset, the MSC infusions appeared to act as a sensitizing stimulus: two of five NHPs receiving MSCs rejected their grafts on belatacept monotherapy with detectable donor-specific antibodies (DSA), and two of four human participants developed de novo DSA or borderline rejection that prevented or reversed immunosuppression withdrawal. The trial was terminated before the third dosing cohort began.
