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Vascularized bone marrow transplantation (VBMT) across a fully allogeneic barrier induces immune chimerism with absence of graft versus host disease (GVHD)
Author(s) -
Strande Louise F,
Lefebvre Daniel,
Tai Chau,
Matthews Martha,
Marra Steven,
Hewitt Charles
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.862.27
Subject(s) - allotransplantation , immunosuppression , medicine , immune system , bone marrow , transplantation , immunology , histology , graft versus host disease , heart transplantation , microchimerism , immune tolerance , pathology , biology , pregnancy , fetus , genetics
Our laboratory developed a model in rats to study cardiac allotransplantation with simultaneous VBMT. We hypothesized VBMT would induce chimerism with the absence of GVHD. Lewis female rats received VBMT (n=9) or VBMT with heterotopic heart transplant (n=5) from ACI male donors. Recipients received 2mg/kg FK506 immunosuppression for 14 days. Sacrifice was electively between 21 to 280 days or at time of heart allograft rejection. To demonstrate chimerism, PCR was performed to identify the donor Y‐specific sequence. None of the rats exhibited clinical signs of GVHD. Four rats expelled the VBMT between days 42 to 201, representing probable technical failure. Remaining rats had no signs of VBMT failure. Histology revealed necrotic bone for the failed VBMTs and areas of viable bone marrow in the successful VBMTs. Two of 5 hearts continued beating up to 280 days. Histology of the cardiac allografts showed viable myocardium. Chimerism was demonstrated in all rats, including the failed VBMTs. We conclude VBMT is capable of inducing chimerism across a fully allogeneic barrier with the absence of GVHD. We hypothesize that VBMT serves as an extra‐thymic site of immune education via it's intricate microstromal network and modulates the host immune response which may then serve as the foundation for solid organ allograft transplantation tolerance induction. Supported by American Heart Association Grant #0555795T.