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

作     者：XIE Hai-yang（谢海洋） HUANG Dong-sheng（黄东胜） JIA Chang-ku（贾长库） ZHENG Shu-sen（郑树森） 

作者机构：Department of Hepatobiliary Pancreatic Surgery Key Lab of Combined Multi-Organ Transplantation Ministry of Public Health First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China 

出 版 物：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 (浙江大学学报（英文版）B辑（生物医学与生物技术）)

年 卷 期：2005年第6卷第12期

页      面：1188-1194页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：Project(No.2003CB515501)supportedbytheNationalBasicRe-searchProgram(973)ofChina 

主　　题：Liver transplantation Rejection Bone marrow infusion Chimerism 

摘      要：Objective： To study the effect and implication ofnonmyeloablative 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-7 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 （10.7i0.5） 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-7 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