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


CONCLUSIONS
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.
Xie
Hai-yang
HY
Department of Hepatobiliary Pancreatic Surgery, Key Lab of Combined Multi-Organ Transplantation, First Affiliated Hospital, Zhejiang University, Hangzhou, China.
Huang
Dong-sheng
DS
Jia
Chang-ku
CK
Zheng
Shu-sen
SS
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods*; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control*; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology*; D016896:Treatment Outcome