IN-UTERO HEMATOPOIETIC STEM-CELL TRANSPLANTS PROLONG SURVIVAL OF POSTNATAL KIDNEY-TRANSPLANTATION IN MONKEYS

The authors hypothesized that in utero transplantation of T-cell-deple ted paternal marrow into rhesus monkey fetuses would induce tolerance to postnatal kidney grafts from the marrow donor. T-cell-depleted pate rnal bone marrow was transplanted intraperitoneally into two female fe tal rhesus monkeys at 61 +/- 1 days' gestation. Chimeric monkeys (n = 2) received kidney transplants from paternal donors. Control monkeys ( n = 2) underwent kidney transplants without prior in utero stem cell t ransplants. Both chimeric monkeys demonstrated low level (<0.1% donor cells) engraftment in the bone marrow and peripheral blood using the p olymerase chain reaction assay for the Y chromosome. The mixed lymphoc yte reaction demonstrated hyporeactivity to the donor. Control animals demonstrated severe acute rejection and graft failure 1 week posttran splant. The first chimeric monkey had no significant clinical or sonog raphic evidence of renal failure until 7 weeks after the transplant. B iopsy findings showed mild rejection 1 week postoperatively, but rejec tion did not significantly progress until 5 weeks later. The second ch imeric monkey had no significant clinical or sonographic changes for 4 weeks, but evidence of moderate rejection was seen on biopsy results. This monkey was given a 10-week course of immunosuppression, and had no clinical or sonographic renal deterioration, although biopsy result s showed chronic rejection that was confirmed when electively euthaniz ed 8 months later. Our data suggest that in utero transplantation of h ematopoietic stem cells can increase the survival of a kidney allograf t in the rhesus monkey. Copyright (C) 1997 by W.B. Saunders Company.