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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1413-1420. Prepublished online as a Blood First Edition Paper on April 25, 2006; DOI 10.1182/blood-2006-02-004341.
Submitted February 16, 2006
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Dept. of Surgery * Corresponding author; email: murase{at}pitt.edu.
Organ allografts have been shown to provide a syngenic microenvironment for organ-based donor hematopoietic stem cells to maintain long-lasting chimerism after transplantation. We hypothesized that organ allografts would also support engraftment and hematopoiesis of adjunctively infused donor marrow stem cells, syngenic to organ grafts, in non-myeloablated recipients. In BN-to-LEW and GFP-to-ACI rat combinations, donor bone marrow (BM) infusion together with small intestinal transplantation (SITx) under short course tacrolimus immunosuppression resulted in persistent macrochimerism (>5%) for 150d. In contrast, after BM infusion or SITx alone, chimerism was temporary and disappeared by 100d. Y-chromosome PCR in sex-mismatched male BM plus female intestine or female BM plus male intestine transplantation into female recipients suggested that persistent macrochimerism was derived from infused BM. BM infusion together with lymphoid-depleted intestinal grafts also supported macrochimerism development; however third-party intestinal grafts did not. After GFP+BM plus WT SITx into ACI, large numbers of GFP+ leukocytes were found in WT intestinal grafts. Isolated cells from WT intestinal grafts developed GFP+ CFU-C and propagated multilineage GFP+ leukocytes when adoptively transferred into lethally irradiated WT recipients. These findings suggest that intestinal allograft supports simultaneously infused donor (syngenic to organ grafts) marrow stem cell engraftment, differentiation and persistence of chimerism.
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