In utero hematopoietic stem cell transplants prolong survival of postnatal kidney transplantation in monkeys.
The authors hypothesized that in utero transplantation of T-cell-depleted paternal marrow into rhesus monkey fetuses would induce tolerance to postnatal kidney grafts from the marrow donor. T-cell-depleted paternal bone marrow was transplanted intraperitoneally into two female fetal 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 transplants. Both chimeric monkeys demonstrated low level (<0.1% donor cells) engraftment in the bone marrow and peripheral blood using the polymerase chain reaction assay for the Y chromosome. The mixed lymphocyte reaction demonstrated hyporeactivity to the donor. Control animals demonstrated severe acute rejection and graft failure 1 week posttransplant. The first chimeric monkey had no significant clinical or sonographic evidence of renal failure until 7 weeks after the transplant. Biopsy findings showed mild rejection 1 week postoperatively, but rejection did not significantly progress until 5 weeks later. The second chimeric 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 results showed chronic rejection that was confirmed when electively euthanized 8 months later. Our data suggest that in utero transplantation of hematopoietic stem cells can increase the survival of a kidney allograft in the rhesus monkey.
Mychaliska
G B
GB
The Fetal Treatment Center, and the Department of Surgery, University of California, San Francisco 94143-0570, USA.
Rice
H E
HE
Tarantal
A F
AF
Stock
P G
PG
Capper
J
J
Garovoy
M R
MR
Olson
J L
JL
Cowan
M J
MJ
Harrison
M R
MR
D000818:Animals; D002678:Chimera; D005260:Female; D005333:Fetus / Q000601:surgery*; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D016030:Kidney Transplantation / Q000276:immunology*; D008253:Macaca mulatta; D011247:Pregnancy; D019172:Transplantation Conditioning / Q000379:methods*