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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Infusion of nonmyeloablative bone marrow alleviates acute rejection reaction in liver allotransplantation

Abstract: Objective: To study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation. Methods: Orthotopic liver transplantation model was used in this study. Groups were set as follows: Group I, syngeneic control (Wistar-to-Wistar); Group II, acute rejection (SD-to-Wistar); Group III, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar+CsA); Group IV, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar+DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed. Histological grades of rejection were determined by pathological examination. IL-2 and IFN-γ level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry). Results: No signs of rejection were found in Group I. Acute rejection occurred in both Group II and the short-term CsA treated group. All the recipients died at (9~15) d posttransplantation with a median survival time of (10.7±0.5) d and (11.2±2.4) d, respectively. Only mild rejection could be seen in Group III. In Group IV, 4 out of 6 recipients had long-term survival (>100 d), the histological grade of rejection was significantly lower than that of Group II, so did the expression level of IL-2 and IFN-γ in both peripheral blood and grafted liver. Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion. Conclusion: Mild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation and prolong survival of liver allotransplantation.

Key words: Liver transplantation, Rejection, Bone marrow infusion, Chimerism


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DOI:

10.1631/jzus.2005.B1188

CLC number:

R657.3

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Received:

2005-06-10

Revision Accepted:

2005-09-27

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