In utero hematopoietic stem cell transplants prolong survival of postnatal kidney transplantation in monkeys

George B. Mychaliska, Henry E. Rice, Alice F. Tarantal, Peter G. Stock, Jan Capper, Marvin R. Garovoy, Jean L. Olson, Morton J. Cowan, Michael R. Harrison

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)976-981
Number of pages6
JournalJournal of Pediatric Surgery
Volume32
Issue number7
DOIs
StatePublished - Jul 1997

Keywords

  • In utero hematopoietic stem cell transplantation
  • Kidney transplantation
  • Tolerance induction

ASJC Scopus subject areas

  • Surgery

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    Mychaliska, G. B., Rice, H. E., Tarantal, A. F., Stock, P. G., Capper, J., Garovoy, M. R., Olson, J. L., Cowan, M. J., & Harrison, M. R. (1997). In utero hematopoietic stem cell transplants prolong survival of postnatal kidney transplantation in monkeys. Journal of Pediatric Surgery, 32(7), 976-981. https://doi.org/10.1016/S0022-3468(97)90381-X