Infusion of nonmyeloablative bone marrow alleviates acute rejection reaction in liver allotransplantation |
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| Authors: | Xie?Hai-yang Huang?Dong-sheng Jia?Chang-ku Email author" target="_blank">Zheng?Shu-sen?Email author |
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| Institution: | (1) Department of Hepatobiliary Pancreatic Surgery, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hanzhou, 31003, China |
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| 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.
Project (No. 2003CB515501) supported by the National Basic Research Program (973) of China |
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| Keywords: | Liver transplantation Rejection Bone marrow infusion Chimerism |
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