Donor-specific unmodified bone marrow transfusion does not facilitate intestinal engraftment after bowel transplantation in a porcine model.
BACKGROUND
The immunosuppression required to prevent rejection of intestinal transplants causes a high rate of infection and lymphoma. It is crucial that immunomodulatory strategies be developed to facilitate intestinal engraftment.


METHODS
We prospectively examined the effect of unpurified donor-specific bone marrow transfusions (DSBMTs) on rejection, infection, graft-versus-host disease (GVHD), and survival after intestinal transplantations in 44 Yorkshire Landrace pigs. Four groups that differed according to presence or abscence of treatment with FK506 and DSBMT were analyzed.


RESULTS
In nonimmunosuppressed pigs, DSBMTs had no effect on survival (8 days versus 9 days in controls; p = 0.9). In FK506 pigs, DSBMTs tended to reduce survival (21 days versus 37 days in FK506 controls; p = 0.1); no difference was seen between two bone marrow dosages 5 x 10(7) or 5 x 10(8) bone marrow cells/kg. No difference in the incidence of death caused by rejection was seen between DSBMTs and controls, but there was a marked tendency toward more deaths caused by rejection in DSBMTs + FK506 versus FK506-only pigs (p = 0.09). Daily stomal assessment showed a higher rate of moderate and severe interstitial rejection in DSBMT + FK506 versus FK506-only pigs; DSBMT was also associated with increased vascular rejection. Finally, groupwise comparison showed an order of susceptibility to lethal GVHD and infection as follows: DSBMT + FK506 > FK506 > DSBMT > controls.


CONCLUSIONS
Rather than promoting engraftment, DSBMT can sensitize recipients and cause rejection after intestinal transplantation. It aggravates the risks of generalized GVHD and infection and tends to reduce graft and recipient survival. Before being applied clinically, DSBMT needs to be refined to increase its tolerogenic potential without causing GVHD.
Pirenne
J
J
Department of Surgery, School of Public Health, University of Minnesota, Minneapolis 55455, USA.
Gruessner
A C
AC
Benedetti
E
E
Troppmann
C
C
Nakhleh
R E
RE
Uckun
F M
FM
Gruessner
R W
RW
D000818:Animals; D016026:Bone Marrow Transplantation; D006084:Graft Rejection / Q000401:mortality / Q000473:pathology; D006086:Graft vs Host Disease / Q000401:mortality / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007239:Infections / Q000401:mortality; D007422:Intestines / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D011183:Postoperative Complications / Q000401:mortality; D016019:Survival Analysis; D013552:Swine; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors; D014019:Tissue Donors
D007166:Immunosuppressive Agents; D016559:Tacrolimus