title: Long-term acceptance of renal allografts following prenatal inoculation with adult bone marrow.
abstract: BACKGROUND
  The aim was to investigate if intravascular in utero injection of adult bone marrow into swine fetuses could lead to macrochimerism and tolerance to the donor.
  
  
  METHODS
  Outbred Yorkshire sows and boars screening negative for MHC allele SLA of MGH miniature swine were bred. A laparotomy was performed on the sows at 50 days gestation to expose the uterus. Bone marrow harvested from SLA miniature swine was T-cell depleted and injected intravascularly into seventeen fetuses. Flow cytometry was performed to detect donor cells (chimerism) in the peripheral blood after birth. Mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML) assays were used to assess the response to donor MHC. Previously frozen skin grafts from the bone marrow donor were placed on the offspring from the first litter. Donor-matched renal transplant from SLA donors were performed on chimeric swine, with and without a short 12-day course of cyclosporine, and one nonchimeric littermate.
  
  
  RESULTS
  Nine inoculated offspring demonstrated donor cell chimerism in the peripheral blood and lymphohematopoietic tissues. All animals with detectable chimerism within the first three weeks were consistently nonreactive to donor MHC in vitro. Animals challenged with donor skin grafts displayed prolonged graft survival without producing antidonor antibodies. All chimeric animals accepted donor-matched kidney allografts, even one without cyclosporine. The kidney in the nonchimeric littermate rejected by day 21.
  
  
  CONCLUSIONS
  Transplantation of allogeneic adult bone marrow into immunocompetent fetal recipients resulted in chimerism. In utero inoculation led to operational tolerance to the donor's major histocompatibility antigens and long-term acceptance to organ allografts.
authors.affiliation: Division of Plastic Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Mathes
authors.forename: Mario G
authors.initials: MG
authors.lastname: Solari
authors.forename: Mark A
authors.initials: MA
authors.lastname: Randolph
authors.forename: G Scott
authors.initials: GS
authors.lastname: Gazelle
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Christene A
authors.initials: CA
authors.lastname: Huang
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D005333:Fetus / Q000601:surgery*; D006085:Graft Survival; D066298:In Vitro Techniques; D016030:Kidney Transplantation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D013552:Swine; D013556:Swine, Miniature; D014019:Tissue Donors; D018183:Transplantation Chimera; D023001:Transplantation Tolerance