自体骨髓干细胞延长小型猪肝移植术后存活的研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:通过非静脉转流方式建立稳定成熟的小型猪原位肝移植急性排斥反应模型。方法:小型猪包括两种小型猪:版纳小型猪(由四川医学科学院实验动物研究所提供);西藏小型猪(由南方医科大学动物研究所提供)。实验分为A、B两组,A组:供体、受体均为中国版纳小型猪,B组:版纳猪作为供体,西藏小型猪作为受体,每一组中的供体和受体随机匹配,在充分熟悉猪肝脏的解剖特点的基础上,进行原位肝移植。在整个实验中供体采用基础麻醉,通过肝动脉及门静脉双灌注方法进行供肝灌注,受体采用气管插管+静脉复合全麻醉。手术前术后测定肝功能(AST,Tbil)、术后观察肝移植后猪的一般状况,存活时间和肝脏组织的病理变化。结果:1、共进行小型猪原位肝移植手术32例,平均手术时间(139.61±14.27)min,平均无肝期(20.28±3.43)min,术中平均失血量359.22±66.91ml,平均输血量410.06±51.13ml,无术中死亡,1例因腹腔出血术后1天死亡,因胆总管吻合口胆瘘术后第5天死亡1例,1例术后3天因肺内感染死亡,另1例术后第7天也因肺内感染死亡。受体死亡后进行解剖未见门静脉及肝动脉狭窄的情况。2、各组受体术后7d成活率分别为A组90.9%,B组70%,14天存活率A组为86.4%,B组受体均在1周左右死亡,14天存活率为0,A组生存时间明显比B组延长(P<0.001);3、α=0.05为检验水准,在术前两组血清AST、Tbil值的比较尚无统计学差异p>0.05,A组和B组中术后的AST总体变化比较有显著的统计学差异(p<0.001,F=15.11);A组和B组中术后的Tbil总体变化比较有显著的统计学差异(p<0.001,F=24.99);术后AST、Tbil在两组中都有升高,A组中AST升高的缓慢术后1天和术后3天比较没有统计学意义(p=0.091),与术后6天比较有统计学意义(p=0.004),术后3天和术后6天的比较没有统计学意义(p=0.82),Tbil升高的缓慢术后1天分别与术后3天、6天比较有统计学意义(p<0.05),术后3天和术后6天比较没有统计学差异(p>0.05);B组中术后AST逐渐升高,不同时间点的变化有显著的统计学意义(P<0.001,F=73.35),术后1天和术后3天的比较无统计学意义(p>0.05),与术后6天的比较有统计学差异(p<0.001),术后3天的和术后6天的比较有统计学差异(p=0.01)。Tbil也是逐渐性升高不同时间点的比较有显著的统计学意义(P=0.001,F=25.58),术后1天的分别与术后3天、6天的比较有统计学差异(p<0.05),术后3天与术后6天比较有统计学意义(p=0.025)。4、病理变化:术后A组移植肝脏中出现了缺血再灌注损伤的病理表现,术后B组移植肝脏中出现严重急性排斥反应,肝组织汇管区大量炎症细胞聚集,部分肝小叶出现坏死。结论:1、成功地建立了成熟稳定的非静脉转流方式的中国小型猪原位肝移植急性排斥反应的模型;2、A组的受体在肝移植后的生存时间明显长于B组中的受体,B组受体移植的肝脏中出现了严重的急性排斥反应,本研究成功的建立了不同封闭群小型猪之间的异体原位肝移植的急性排斥反应模型;3、非静脉转流方式在小型猪原位肝移植中是可行的。
     目的:在已建立的小型猪原位肝移植急性排斥反应模型的基础上,研究在术中经门静脉输注经BrdU标记的自体骨髓干细胞在移植肝中的分化状况和对受体长期存活影响。方法:非静脉转流的方式建立小型猪的原位肝移植急性排斥反应的模型,供体猪为版纳小型猪(由四川医学科学院实验动物研究所提供),受体猪均为西藏小型猪(由南方医科大学动物研究所提供),实验分为两组,对照组(在第一部分实验中,从B组的10例受体中随机抽取8例作为第二部分的对照组)和处理组,提前抽取处理组受体猪的骨髓血,分离培养获得骨髓干细胞并经BrdU标记,对照组仅行原位肝移植,处理组在原位肝移植的基础上,在术中经门静脉输注标记好的受体自身骨髓肝细胞,术后14天、28天,取病理组织活检观测移植细胞的分化状况和功能,同时在受体麻醉后开腹术前,术后1天、3天、6天采静脉血检测肝功能的变化(AST、ALT),并观测猪的一般状况和生存时间及病理变化。结果:1、处理组中BrdU标记细胞的阳性率在移植后14天、28天分别为31.70±1.79%,33.85±1.99%,两者之间比较没有统计学差异(P>0.05);2、BrdU标记细胞和白蛋白染色双阳性率在术后14天、28天分别为28.53±1.28%,30.42±1.59%,两者之间无统计学意义(P>0.05)。这说明BrdU标记的受体自身骨髓干细胞在移植的肝脏微环境中发育分化为肝细胞,并具有生物学活性,能够分泌白蛋白;3、生存状况:两组中位生存时间(Mediansurvival time,MST)分别为:对照组7d,处理组32d,处理组明显比对照组的生存时间延长P<0.001。对照组中的受体一般都在1周左右死亡,而处理组中的受体大多数能够存活1个月左右;4、肝功能变化:α=0.05为检验水准,(1)术前两组血清AST、ALT值的比较尚无统计学差异(p>0.05),处理组和对照组中AST总体变化比较有显著的统计学差异(p=0.002,F=7.626);处理组和对照组中ALT总体变化比较有显著的统计学差异(p=0.002,F=8.877);(2)术后AST、ALT在两组中都有升高,处理组中AST在不同时间点的变化有统计学意义(p<0.001,F=123.15),术前AST变化分别与术后不同时间点的变化比较有统计学意义(p<0.05);处理组中ALT升高的缓慢术后1天分别与术后3天、6天比较有统计学意义(p<0.05),术后3天和术后6天比较没有统计学差异(p>0.05);(3)对照组中AST术后逐渐升高,不同时间点比较有显著统计学意义(P<0.001,F=46.64).术后1天与术后6天的比较有统计学差异(p=0.001),术后3天和术后6天比较有统计学差异(p=0.017).ALT也是逐渐性升高不同时间点的比较有显著的统计学意义(P<0.001,F=41.80),术后1天的分别与术后3天、6天的比较有统计学差异(p<0.05);5、组织病理变化:术后两组均出现不同程度的免疫排斥反应,对照组在术后3天移植的肝脏中出现汇管区大量炎症细胞聚集,主要是淋巴细胞,炎症反应重,肝细胞浑浊,气球样变性并出现不同程度的点状、灶状坏死,而处理组在术后3天病理活检见:大致呈正常肝脏病理,肝组织轻度淤血,血管周围少量炎性细胞浸润,少数汇管区小静脉或肝静脉内皮细胞下淋巴细胞浸润,肝细胞点状坏死,中性粒细胞浸润。结论:1、自体骨髓干细胞延长了受体的存活时间;2、能够在移植肝脏中分化为肝细胞,并产生白蛋白;3、减轻免疫排斥反应,保护移植的肝脏免受损害,门静脉输注自体骨髓干细胞可能是减轻排斥反应、延长受体生存时间的机制。
Objective:To establish stable china minitype pig orthotopic liver transplantation acute rejection model by non-vein by -pass method.Method: Chinese miniature pigs includ Barman pigs buyed from experimental animal research center of Sichuan Academy of Medical Science and xizang pigs buyed from experimental animal research center of Southen Medical College,there are two groups,A group and B group,in A group:donors and receptors are all banna minitype pigs.in B group: donors are banna mintype pigs and receptors are Tibet minitype pigs,donors and receptors are matched randomly in each groups,during the experiment time,we have an intimate knowledge of pig liver dissection,all donors are accepted basis narcosis and all receptors accepted tracheal intubation +vein multiplicity narcosis in the experiment.Donor's liver is perfused by hepatic artery and portal vein.we determined liver biochemistry before operation and after operation one day,three day and six day.receptor's condition survival time and liver tissues of pathological change are observed.Result:32 orthotopic liver transplantation are carried out, average operational time is 139.61±14.27)min,average anhepatic phase is (20.28±3.43)min,the average volume of blood loss in the operation is 359.22±66.91ml,the average of blood transfusion is 410.06±51.13ml,no death occurred in the operation,one receptor died at the first day after operation because abdominal cavity haemorrhage,one died 3 days later because of lung infection,another two died 5days later and 7days later because of biliary fistula at the common bile duct stoma,no death occurred by portal vein and arterial stenosis.2、receptor 7 days survival rate after operation in A group is 90.9%,in B group is 70%,14days survival rate after operation in A group is 86.4%,in B group all receptors almost die during 7 days,14 days survival rate is 0,statistics significance is obverse in A group (P<0.001).3.α=0.05 as the size of test,AST and Tbil comparison in the two groups are no statistics significance before operation(p>0.05),but they all increase obviously after operation,especially in B group,AST total changes after operation in each group comparison are statistics significance(p<0.001,F=15.11),Tbil total changes in each group comparison are statistics significance(p<0.001,F=24.99),after operation AST,Tbil in two groups have different degree augmentation.In A group: AST increase slowly,the changes in 1day and 3day after operation comparison is no statistics significance(p=0.091),compared with 6day's has a obvious statistics significance(p=0.004),the 3 day's comparing with the 6day's is no statistics significance(p=0.82).Tbil increase slowly,the changes of Tbil in 1day compared with 3day's and 6day's after operation comparison is no statistics significance(p<0.05),3day's compared with 6day's has no statistics significance (p>0.05);in B group:the changes of AST after operation gradually increase,comparisons among different time have an obvious statistics significance (p<0.001,F=73.35),the change in 1day compared with 3day's has no statistics significance(p>0.05),compared with 6day's has statistics significance p<0.001,3day's comparing with 6day's has statistics significance(p=0.01).the changes of Tbil after operation gradually increase,comparisons among different time have an obvious statistics significance(p=0.001,F=25.58),the change in 1day compared with 3day's has statistics significance p<0.05,compared with 6day's has statistics significance(p<0.05),3day's comparing with 6day's has statistics significance(p=0.025).4.pathological change:in A group shows ischemical reperfusion injury in Transplanted liver.receptors in B group occur obviously severely acute rejection after operation,many inflammatory cells aggregate hepatic tissue header domain.Some parts of hepatic lobule appear cellular necrosis.
     Conclusion:1.We have successfully established maturely stable china minitype pig orthotopic liver transplantation acute rejection model by non-vein by -pass method. 2.In A group receptor has an obviously longer survival time than that in B group, receptors in B group show severely acute rejection in transplanted liver,we successfully set up acute rejection model of orthotopic liver transplantation in minitype pigs between different closed population.3.Non-vein by -pass method is feasible to establish china minitype pig Orthotopic liver transplantation model.
     Objective To study receptor's autologous bone marrow stem cell which isolated culture and labeled by BrdU,which injected slowly into portal vein during the operation differentiation condition in Transplanted liver,and long-term survival influence for receptor,on the base of orthotopic liver transplantation in china miniature pigs.Method:establishing orthotopic liver transplantation acute rejection model in china miniature pigs by non -vein by-pass method,donor and receptors are banna pigs(buyed from experimental animal research center of Sichuan Academy of Medical Science)and Tibet pigs(buyed from experimental animal research center of Southen Medical College)respectively,we collected receptor's bone marrow in treatment group 14days ago before operation,and isolated,cultured bone marrow stem cells,at the same times we labeled these cells by BrdU,.experimentation set up the control group(we randomly get 8 examples from 10 examples in the first part B group as the control group)and the treatment group,we only practice orthotopic liver transplantation in the control group,the treatment group also accepts orthotopic liver transplantation,but we inject receptor's autologous bone marrow stem cell labeled by BrdU into portal vein during the opertation.14days 28days after operation,we anesthetize receptor and get a little of liver tissue,making patho-biopsy to observe transplanted cells's differentiation condition and function in Transplanted liver,at the same times we detect Liver function(AST,ALT)before operation and 1day,3days 6days after orthotopic liver transplantation,and observe receptor's general condition,survival time and pathological change of the liner tissue. Result:the cells labeled by BrdU masculine rate in treatment group at 14days and 28days after orthotopic liver transplantation shows 31.70±1.79%and 33.85±1.99% respectively,and there are no statistical significance between that two time point (P>0.05).2.in the receptor's liver tissue the cells labeled by BrdU and albumin dyeing by immunohistochemistry SP method,express both masculine,the rate is 28.53±1.28%on 14days after operation,and 30.42±1.59%on 28days after operation,there are no statistical significance between them(P>0.05).this shows that the receptor's bone marrow stem cells labled by BrdU can grow and differentiate into hepatic cell in liver microenvironment,and have biologic activity,sereting albumin;3.living condition:Median survival time in control group is 7days and 32days in treatment group,we can see that receptor in treatment group has a longer live time than that in the control group(P<0.0001).in B group receptors die about lweek later,in A group receptor can live about lmonth;4.liver metergasis in two group:α=0.05 as the size of test.(1)After orthotopic liver transplantation,hepatic tissue incurs different degree damage,in treatment group this happens more lightly than that in control group, before operation we detected Tibet pig receptor's AST,ALT in the blood,and found the level of each them is almost the same,there are no statistical significance between them p>0.05,but they have different degree augmentation after operation, AST total changes in two group comparison have statistics significance p=0.002,F=7.626,ALT total changes in two group comparison have obviously statistics significance p=0.002,F=8.877.(2)In treatment group:the changes among different time have statistics significance p<0.001,F=123.15,the change of AST before operation compared with different time after operation has statistics significance p<0.05.ALT in treatment group increase slowly,after operation 1day's compared with 3day's and 6day's has statistics significance p<0.05,3day's compared with 6day's is no statistics significance p>0.05.(3)In control group AST gradually increase after operation,comparison among different time have obviously statistics significance p<0.001,F=46.64.1day compared with 6day's have statistics significance p=0.001,3day's compared with 6day's have statistics significance p=0.017.ALT gradually increase after operation,comparison among different time have obviously statistics significance p<0.001,F=41.80,after operation 1day's compared with 3day's and 6day's has statistics significance p<0.05.5,pathological change:after operation there has different degree immunological rejection in two groups,but receptor in control group express severely immunological rejection, Inflammatory reaction is more critical,a lot of lymphocyte aggregate in the header domain in the Transplanted liver,hepatic cell turbid and ballooning degeneration,we find large lobe cellular necrosis,in the treatment group pathological changes 3days after operation show:roughly normal liver tissue,hepatic tissue has a little congestion,a little inflammatory cell infiltrate around blood vessel,we can see lymphocyte infiltration below endothelial cell of small vein or hepatic vein,liver cell shows punctiform cellular necrosis,neutrophile granulocyte infiltrate.
     Conclusion:1.autologous bone marrow stem cell injected into portal vein during the orthotopic liver transplantation can prolong receptor's life;2.these stem cells can differentiate mature liver cell in the hepatic tissue and produce albumin;3.these differentiation cells can lessen immunological rejection and protect transplanted liver,and be the possible mechanism.
引文
1、Starzl TE,Groth CG,et al.Orthotopic liver transplantation of human live.Ann Surg,1968,168:39-42
    2、Kwan Man,Chung-Mau Lo,Irene Oi-Lin Ng,Yong-Chuan Wong,etal,_Liver Transplantation in Rats Using Small-for-Size Grafts.Arch Surg.2001,136:280-285.
    3、卿德科,韩本立,董家鸿,郑树国,冷建军等 小型猪原位肝移植的建立和评估,消化外科杂志,2003年第2卷第5期314-317。
    4、马玉奎,罗义刚,卫培林.猪-人异种肝脏移植在生化和解剖中的可行性初步研究.华西医学,1999;14(1):111-112
    5、詹纯列,徐本法,白朝辉,小型猪及医学实验应用概述。华南国防医学杂志,2001年15卷2期:24-28。
    6、宿华威,韩德恩,李玉兰.家猪肝脏劈离的应用解剖学研究.解剖学杂志,2002;25(2):187-189
    7、蒲淼水,钟世镇,石瑾-猪活体肝脏移植的应用解剖.中国临床解剖学杂志,2003;21(1):74-75
    8、王荞 全学模 肖江卫 金先庆,超声监测大鼠肝移植模型建立的实验研究中国超声医学杂志,2006年07期:490-492。
    9、李涛 唐华美 孙星 彭志海重建肝动脉大鼠肝移植模型的建立 肝脏,2005年03期:221-222。
    10、 Yasushi Koike,Yasushi Adache,Yasuhiro Suzuki,etal, Allogeneic Intrabone Marrow-Bone Marrow Transplantation plus Donor Lymphocyte Infusion Suppresses Growth of Colon Cancer Cells Implanted in Skin and Liver of Rats. Stem Cells Vol. 25 No.2 February 2007: 385-391
    11、 Schon MR, Kollmar O, Wolf S, et al. Liver transplantation after organ preservation with normothermic extracorporeal perfusion. Ann Surg, 2001;233(1):114-123
    12、 Nowak G, Ungerstedt J,Wernerman J,et al.Metabolic changes in the liver graft monitored continuously with microdialysis during liver transplantation in a pig model. Liver Transpl,2002, 8(5):424-432
    13、 Saad S, Minor T, Kotting M, et al. Extention of tolerance of pcrcine liver by cold preservation including postconditioning with gaseous oxygen. Transplantation, 2001;71(4):498-502
    14、Budd JM, Isaac Jl, Bennett J, et al. Morbidity and mortality associated with large-bore percutaneous venovenous bypass cannulation for 312 orthotopic liver transplantations. Liver Transpl, 2001;7(4):359-362
    13、 Camichael FJ, Lindop MJ, Faman JV, et al. Anesthesia for hepatic transplantation: cardiovascular and metabolic alteration casued during orthotopic liver transplantation and their management. Anesth Analg,1985, 64(2): 108-111
    16、 TojimbaraT, Fuchinous S, Sannomiya A, et al, Porcine liver transplantation from non-heart-beating cadaver donors effect of passive/active venovenous bypass on graft function [J], Transplant Proc, 2000, 32 (7): 1626-1627;
    17、郑树森,梁廷波,经典原位肝移植中的转流与非转流[J],2002,1(4):229;
    18、 Lopez-Santamaria M, Migliazza L, Supraceliac aortic clamping during the anhepatic phase of experimental orthotopic liver transplantation [J], J Pediatr Surg 1999, 34 (9): 1374-1377.) 19、 Oike F, Uryuhara K, Otsuka M, et al.Simplified technique of orthotopic liver transplantation in pigs.Transplantation,2001;71(2):328-31
    
    20 郑树国,董家鸿,冷建军,等.猪原位肝移植模型改进的研究.消化外科,2004:3(6):435-438
    21 汤黎明,王杰,钱峻,等.无静脉转流原位肝移植模型的建立.中华实验外科杂志,2004;21(11):1399
    22、祝哲城,彭志海,9例次猪原位肝移植的手术分析,复旦学报,2002,29(3):228-229.
    23、宿华威,韩德恩,李玉兰.家猪肝脏劈离的应用解剖学研究.解剖学杂志,2002;25(2):187-189
    24、刘蔚东,张阳德,龚连生,等.40例猪原位肝移植成功率分析.中国现代医学杂志.2002;12(8):13-16。
    25、李玉民,石彬,李讯,等.47例猪肝移植手术分析.肝胆外科杂志,2004;12(5):378-380
    26、郑树森主编.肝脏移植.北京:人民卫生出版社,2001,129-135
    27、王孟龙,徐冠南,丁国善,等.猪原位肝移植中动脉重建方式探讨.中华器官移植杂志,2001;21(1):57-59
    28、叶晟,韩本立,董家鸿.大鼠原位肝移植的显微外科技巧.中华显微外科杂志,2003;26(1):49-50
    29、郑树国,冯晓彬,董家鸿,等.小型猪原位肝移植的外科技巧及术中管理.第三军医大学学报,2005;27(2):150-153
    30、古维立,庄思敏,尚东,等.肝移植中胆总管重建的术式探讨.广东医学,2002:23(8):799-800
    31、Oike F,Uryuhara K,Otsuka M,et al.Simplified technique of orthotopic liver transplantation in pigs.Transplantation,2001,71(2):328-31
    32、Zimmermann FA,Butcher GW,Davies HS,et al.Techniques for orthotopic liver transplantation in the rat and some studies of the immunologic responses to fully allogeneic liver grafts.Transplant Proc,1979,11:571-574
    33、 Williams IN, Peters TG, Vera SR, et al.Biopsy-directed immuno-suppression following hepatic transplantation. Transplantation, 1985, 39:389.
    1、Starzl TE,Groth CG,Brettschneider L,et al.Orthotopic homotransplantation of the human liver.Ann Surg,1968,168:392-415.
    2、Isme de Kleer,Bas Vastert,Mark Klein,Gi js Teklenburg,Get irkestei jn,Gisella Puga Yung,etal.Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4~+CD25~+ immune regulatory network.Blood,15 February 2006,Vol.107,No.4,pp.1696-1702.
    3、Wekerle T,Kurtz J,Ito H,et al.Allogeneic bone marrow transplantation with co- stimulatory blockade induces microchimerism and tolerance without cytoreductive host treatment.Nature Med,2000,6:464-469.
    4、Nader Na jafian,Monica J.Albin and Kenneth A.Newell,et al.How Can We Measure Immunologic Tolerance in Humans? J Am Soc Nephrol 17:2652-2663,2006
    5、Indira Guieria~1 and Mohamed H.Sayegh.Maternal Acceptance of the Fetus:True Human Tolerance.The Journal of Immunology,2007,178:3345-3351.
    6、Jakub Tolar,Matthew J.O'Shaughnessy,Angela Panoskaltsis-Mortari,Ron T.McElmurry.Host factors that impact the biodistribution and persistence ofmultipotent adult progenitor cells,Blood,15 May 2006,Vol.107,No.10,pp.4182-4188.
    7、Goodell MA,Jackson KA,Majka SM,et al.Stem cell plasticity in muscle and bone marrow.Ann NY Acad Sci,2001,938:208-218
    8、Yuehua Jiang,MD,April Breyer,Laura Lien,BS,Mark Blackstad,etal.Culture of Multipotent Adult Progenitor Cells(MAPCs).Blood(ASH Annual Meeting Abstracts)2004 104:2329-2335
    9、Ruth Williams.Cell replacement therapy-are MAPCs the answer? The Journal of Experimental Medicine,2007,Vol.204,No.1,4a-4
    10、Rao MS,Mattson MP.Stem cells and aging:expanding the possibilities.Mech Aging Dev,2001,122:713-734.
    11、Lindolfo da Silva Meirelles,Pedro Cesar Chagastelles,Mesenchymal stem cells reside in virtually all post-natal organs and tissues.Journal of Cell Science 119,2204-2213(2006)
    12、Marta Serafini~1,Scott J.Dylla~3,Masayuki Oki~1,Yves Heremans,et al.Hematopoietic reconstitution by multipotent adult progenitor cells:precursors to long-term hematopoietic stem cells.The Journal of Experimental Medicine,2006,Vol.204,No.1,129-139
    13、Weissman IL.Translating stem and progenitor cell biology to the clinic:barriers and opportunities.Science,2000,287:1442-6.
    14、Moustapha Kassem.Potential Therapy for Age-Related Diseases.Ann.N.Y.Acad.Sci.1067:436-442(2006).
    15、郭启仓,刘志勇,李占青,张宇等人,5-溴脱氧尿嘧啶核苷标记骨髓间充质干细胞的技术探讨.华北煤炭医学院学报 2004年1月第6卷第1期:4-6.
    16、冯善伟,姚晓黎,李中,柳太云等人,BrdU体外标记大鼠骨髓间充质干细胞的研究.第一军医大学学报,2005,25(2)184-186.
    17、Starzl TE,Groth CG,Brettschneider L,et al.Orthotopic homotransplantation of the human liver.Ann Surg,1968,168:392-415.
    18、Starzl,T. E, Murase N. Microchimerism, macrochimerism, and tolerance. Clin. Transplant, 2000, 14:351-354.
    19、Eun-Woo Lee, Yurong Lai, Huixia Zhang, and Jashvant D. Unadkat. Identification of the Mitochondrial Targeting Signal of the Human Equilibrative Nucleoside Transporter 1 (hENTl). J. Biol. Chem., Vol. 281, Issue 24, 16700-16706, June 16, 2006
    20、Starzl T. E, et al. The lost chord: microchimerism and allograft survival. Immunol Today, 1996, 17:577-584.
    21、Gleit ZL, Fuchimoto Y, Yamada K, et al. Variable relationship between chimerism and tolerance after hematopoietic cell transplantation without myelosuppressive conditioning. Transplantation, 2002, 15:1535-44.
    22、Beschorner WE, Sudan DL, Radio SJ, et al. Heart xenograft survival with chimeric pig donors and modest immune suppression. Ann Surg, 2003, 237:265-72.
    23、Laconi S, Pillai S, Porcu PP et al. Massive liver replacement by transplanted hepatocytes in the absence of exogenous growth stimuli in rats treated with retrorsine, 2001, 158(2):771-777
    24、Rhonda Simper-Ronan, Kate Brilliant, Donna Flanagan, Marie Carreiro, et al. Cholangiocyte marker-positive and -negative fetal liver cells differ significantly in their ability to regenerate the livers of adult rats exposed to retrorsine. Development 133, 4269-4279 (2006)
    25、Anna Mae Diehl.Recent Events in Alcoholic Liver Disease V. Effects of ethanol on liver regeneration. Am J Physiol Gastrointest Liver Physiol, Jan 2005; 288: G1-G6.
    26、Malhi H, Annamaneni P, Slehria S, et al. Cyclophoaphamide disrupts hepatic sinusoidal endothelium and improves tralsplanted cell engraftment in rat liver. Hepatology, 2002, 36: 112-121.
    27、Harald Schrem, Jürgen Klempnauer and Jürgen Borlak. Liver-Enriched Transcription Factors in Liver Function and Development. Part II: the C/EBPs and D Site-Binding Protein in Cell Cycle Control, Carcinogenesis, Circadian Gene Regulation, Liver Regeneration, Apoptosis, and Liver-Specific Gene Regulation. Pharmacol Rev 56:291-330, 2004.
    28、Felix C. Popp, Przemyslaw Slowik, Elke Eggenhofer, Phillip Renner, et al, No Contribution of Multipotent Mesenchymal Stromal Cells to Liver Regeneration in a Rat Model of Prolonged Hepatic Injury. Stem Cells Vol. 25 No. 3 March 2007, pp. 639-645
    29、M. Bilotas, R.I. Baranao, R. Buquet, C. Sueldo, M. Tesone and G. Meresman. Effect of GnRH analogues on apoptosis and expression of Bcl-2, Bax, Fas and FasL proteins in endometrial epithelial cell cultures from patients with endometriosis and controls. Human Reproduction 2007 22(3):644-653
    30、 Guha C, Sharma A, Gupta S, et al. Amelioration of radiation-induced liver damage in partially hepatectomized rats by hepatocyte transplantation. Cancer Res, 1999, 59: 5871-5874.
    31、 Choi D, Oh HJ, Chang UJ, et al. In vivo differentiation of mouse embryonic stem cells into hepatocytes. Cell Transplantation, 2002, 11: 359-368.
    32、 Hiroaki Shibata, Naohide Ageyama, Yujiro Tanaka' Yukiko Kishi, et al. Improved Safety of Hematopoietic Transplantation with Monkey Embryonic Stem Cells in the Allogeneic Setting. Stem Cells Vol. 24 No. 6 June 2006, pp. 1450-1457
    33、 Takashi Yazawa, Tetsuya Mizutani, Kazuya Yamada, Hiroko Kawata, et al. Differentiation of Adult Stem Cells Derived from Bone Marrow Stroma into Leydig or Adrenocortical Cells.Endocrinology,2006,Vol.147,No.
    9 4104-4111
    
    34、Dolores Baksh,Raphael Yao,Rocky S.Tuan,et al.Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow.Stem Cells,Mar 2007;10.1634.
    35、Sarah Snykers,Tamara Vanhaecke,Peggy Papeleu,Aernout Luttun.et al,Sequential Exposure to Cytokines Reflecting Embryogenesis:The Key for in vitro Differentiation of Adult Bone Marrow Stem Cells into Functional Hepatocyte-like Cells.Toxicological Sciences 200694(2):330-341
    36、Tong Ming Liu,Monique Martina,Dietmar W.Hutmacher,James Hoi Po Hui,et al.Identification of Common Pathways Mediating Differentiation of Bone Marrow- and Adipose Tissue-Derived Human Mesenchymal Stem Cells into Three Mesenchymal Lineages.Stem Cells Vol.25 No.3 March 2007,pp.750-760
    37、Atsunori Nakao,Hideyoshi Toyokawa,Kei Kimizuka,Michael A.Nalesnik,et al.Simultaneous bone marrow and intestine transplantation promotes marrow-derived hematopoietic stem cell engraftment and chimerism.Blood,15 August 2006,Vol.108,No.4,pp.1413-1420.
    38、Arkadopoulos N,Lilja H,Suh KS,et al.Introsplenic transplantation of allogenic hepatocytes prolongs survival in anhepatic trts.Hepatology,1998,1365-1370
    39、Emerson RW.Human hepatocyte transplantation:gene therapy and more?Pediatrics,1998,102:647-648
    40、Strom SC,Fisher RA,Thompson MT,et al.Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver faclure. Transplantation, 1997, 63:559-569
    41、 Grompe M. Liver repopulation for the treatment of metabolic diseases. J Inherit Metab Dis, 2001, 24:231-44.
    42、 Yiannis Kailis , Malcolm R Alison ~2and Stuart John Forbes,et al. Bone marrow stem cells and liver disease. Gut, Dec 2006; 10.1136.
    43、 Roberto M. Lemoli, Lucia Catani, Simona Talarico, Elisabetta Loggi, et al, Mobilization of Bone Marrow-Derived Hematopoietic and Endothelial Stem Cells After Orthotopic Liver Transplantation and Liver Resection. Stem Cells Vol. 24 No. 12 December 2006, pp. 2817-2825
    44、Jan Schulte am Esch, II~a, Wolfram Trudo KnoefeP, Michael Klein, et al, Portal Application of Autologous CD133~+ Bone Marrow Cells to the Liver: A Novel Concept to Support Hepatic Regeneration. Stem Cells 2005;23:463-470.
    45、 Shapiro R , Rao AS , Corry RJ , et al . Kidney transplantation with bone marrow augmentation: five-year outcomes [J]. Transplant Proc,2001 ;33 :1134
    46、 George V. Mazariegosa, Alan F. Zahorchak, Jorge Reyes, Lynn Ostrowski, Bridget Flynn, Adriana Zeevib and Angus W. Thomson, Dendritic Cell Subset Ratio in Peripheral Blood Patients. American Journal of Transplantation 2003; 3: 689-696
    47、 Ming Zhang, Quanxing Wang, Yushan Liu, Yanping Sun, Guoshan Ding Zhiren Fu , et al, Effective induction of immune tolerance by portal venous infusion with IL-10 gene-modified immature dendritic cells leading to prolongation of allograft survival. J Mol Med (2004) 82:240-249
    48、Fred Fandrich, Bettina Dresske ,Michael Bader ,Maren Schulze, Embryonic stem cells share immune-privileged features relevant for tolerance induction. J Mol Med (2002) 80:343-350
    49、James M, Mathewa, Rolando 0, Garcia-Moralesa, Manuel Carrenoa, Yide Jin, Laphalle Fuller, Bonnie Blomberg,et al , Immune responses and their regulation by donor bone marrow cells in clinical organ transplantation. Transplant Immunology 11 (2003) 307-321
    50、James A, Martin, Yazan Duwayri, Gilbert Falcon, etal, Impact of Aging on Rat Bone Marrow-Derived Stem Cell Chondrogenesis. Biological Sciences and Medical Sciences, 2007, 62: 136-148
    51、 Quanjun Cui, Zengming Xiao, Xudong Li, Khaled J. Saleh, et al, Use of Genetically Engineered Bone-Marrow Stem Cells to Treat Femoral Defects: An Experimental Study, The Journal of Bone and Joint Surgery (American). 2006, 88:167-172.
    52、 Ciancio G, Burke GW, Moon J, Garcia-Morales R, RosenA, etal, Donor bone marrow infusion in deceased and living donor renal transplantation. Yonsei Medical Journal 2004, 45 (6): 998-1003.
    53、 Susumu Ikehara Intra-bone Marrow-Bone Marrow Transplantation: A New Strategy for Treatment of Stem Cell Disorders. Ann. N. Y. Acad. Sci. 2005, 1051: 626-634.
    54、 XinyangHu, Jianan Wang, Jie Chen, Ronghua Luo, etal Optimal temporal delivery of bone marrow mesenchymal stem cells in rats with myocardial infarction . Eur J Cardiothorac Surg 2007, 31:438-443.
    55、 Takashi Yazawa, Tetsuya Mizutani, Kazuya Yamada, Hiroko Kawata, etal, Differentiation of Adult Stem Cells Derived from Bone Marrow Stroma into Leydig or Adrenocortical Cells. Endocrinology, 2006, Vol. 147, No. 9 .4104-4111.
    56、 Vincent Donckier, Roberto Troisi, Michel Toungouz Isabelle Colle, Hans Van Vlierberghe, etal, Donor stem cell infusion after non-myeloablative conditioning for tolerance induction to HLA mismatched adult living-donor liver graft Transplant Immunology 13(2004)
    139-146.
    
    57、赵若辉 综述 范 健 审校,肝细胞移植进展.J ou rnal of H ep atobiliary S u rg ery,2000,V ol.8,N o.2
    58、Pankaj R,A ndrew K,Kuldeep K et al.Studies of liver repopulationusing the dipep tidyl pep tidase I - deficient rat and o ther rodentrecip ients;cell size and structure relationsh ip s regulate capacity fo rincreaser transp lanted hepatocyte mass in the liver lobule.H e atology,1996,23(3):482.
    59、Pankaj R,A ndrew K,Kuldeep K et al.Studies of liver repopulation using the dipep tidyl pep tidase I - deficient rat and o ther rodent recip ients;cell size and structure relationsh ip s regulate capacity fo r increaser transp lanted hepatocyte mass in the liver lobule.H ep atology,1996,23(3):482.
    60、Avital I,Feraresso C,Aoki T,Hui T,Rozga J,Demetriou A,Muraca M.Bone marrow-derived liver stem cell and mature hepatocyte engraftment in livers undergoing rejection.Surgery,2002,132(2):384-90.
    61、余宏铸,黄洁夫,陈规划,等.TNF-β在大鼠同种异体肝移植急性排斥反应中的表达.肝胆外科杂志,1998,6(2):120.
    62、李晓华,胶体金标记技术及应用.生物学通报.2004年第39卷12期:54-55
    63、王存邦,鸥英贤,白海,基因标记技术研究及应用.中国现代医学杂志,2002年死12卷5期:41-43.
    64、杨春青,张炜明,李百周,免疫组化与原位杂交双标记技术的方法学研究.南京医科大学学报,2004年死24卷3期:316.
    65、Hou LL,Zheng M Pei XT,et al.Migration and differentiation of human bone marrow mesenchymal stem cells in the rat brain.Acta Physiologica Sinica,2003,55(2):153-159
    66、郑树森.肝脏移植.第一版.北京:人民卫生出版社,2001.454-455.
    67、Mcdowell EM,Zhang XM and Desnati AM,Localization of healing tracheal wounds using bromodeoxyuridine immunohistochemistry.Stain rechnol,1990,65:25-29
    68、晏炬.单克隆抗体技术.国外医学分子生物学分册,1993,15:72-75.
    69、Eiji Mizutani,Hiroshi Ohta,Satoshi Kishigami,Nguyen Van Thuan,et al,Developmental ability of cloned embryos from neural stem cells.Reproduction(2006)132 849-857
    70、Thomson JA,Itskovitz-Eldor J,Shapiro SS,et al.Embryonic stem cell lines derived from human blastocysis.Science,1998,282:114-117
    71、Kat ja Schenke-Layland,Ekaterini Angelis,Katrin E.Rhodes,et al.Collagen Ⅳ induces trophoectoderm differentiation of mouse embryonic stem cells.Stem Cells,Mar 2007;10.1634
    72、Sophielev,Izhak Kehat and Lior Gepstein.Differentiation Pathways in Human Embryonic Stem Cell-Derived Cardiomyocytes.Ann.N.Y.Acad.Sci.1047:50-65(2005).
    73、Robert David,Michael Groebner,Wolfgang-Michael Franz,et al.Magnetic Cell Sorting Purification of Differentiated Embryonic Stem Cells Stably Expressing Truncated Human CD4 as Surface Marker.Stem Cells 2005;23:477-482
    74、Maria Beatriz Herrera,Stefania Bruno,Stefano Buttiglieri,et al,Isolation and Characterization of a Stem Cell Population from Adult Human Liver,Stem Cells Vol.24 No.12 December 2006,pp.2840-2850.
    75、Frankel MS.In search of stem cell policy.Science,2000,287:1397.
    76、Stuart Forbes,Pamela Vig,Howard Thomas,et al.Hepatic stem cell.J Pathology,2002,197:510-518
    77、Theise ND,Saxena R,Portmann BC,et al.The canal of Hering and hepatic stem cells in humans.Hepatology,1999,30:1425-1433.
    
    78、Neil M.Masson,Ian S.Currie,John D.Terrace,O.James Garden,et at,.Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1.Am J Physiol Gastrointest Liver Physiol 291:G45-G54,2006;
    79、Carl R.Walkley and Stuart H.Orkin.Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells.PNAS,Jun 2006;103:9057-9062..
    80、Michael Oertel,Anuradha Menthena,Yuan-Qing Chen,David A.Shafritz Properties of Cryopreserved Fetal Liver Stem/Progenitor Cells That Exhibit Long-Term Repopulation of the Normal Rat Liver_Stem Cells Vol.24 No.10 October 2006,pp.2244-2251
    81、Tailoi Chan-Ling,Louise Baxter,Aqeela Afzal,et al,Hematopoietic Stem Cells Provide Repair Functions after Laser-Induced Bruch' s Membrane Rupture Model of Choroidal Neovascularization.American Journal of Pathology.2006,168:1031-1044.
    82、Goodell MA,Jackson KA,Majka SM,et al.Stem cell plasticity in muscle and bone marrow.Ann NY Acad Sci,2005,938:208-218.
    83、Almeida-Porada G,Porada C,Zan jani ED.Adult stem cell plasticity and methods of detection.Rev Clin Exp Hematol,2001,5:26-41.
    84、Evangelos Dalakas,Philip N.Newsome,David J.Harrison,et al.Hematopoietic stem cell trafficking in liver injury.The FASEB Journal.2005,19:1225-1231.
    85、Rao MS,Mattson MP.Stem cells and aging:expanding the possibilities.Mech Aging Dev,2004,122:713-734.
    86、Jeong-Ho Hong,Eun Sook Hwang,Michael T.McManus.et al.TAZ,a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation.Science 12 August 2005:Vol.309.no.5737,pp.1074-1078,
    87、 Miura K, Nagai H, Ueno Y, Goto T, Mikami K, Nakane K, Yoneyama K, Watanabe D, Terada K, Sugiyama T, Imai K, Senoo H, Watanabe S. Epimorphin is involved in differentiation of rat hepatic stem-like cells through cell-cell contact. Biochem Biophys Res Commun, 2006, 311(2):415-23.
    88、 Wang X, Ge S, McNamara G, Hao QL, Crooks GM, Nolta JA. Albumin-expressing hepatocyte-like cells develop in the livers of immune-deficient mice that received transplants of highly purified human hematopoietic stem cells. Blood, 2003, 101(10):4201-8.
    89、 Okumoto K, Saito T, Hattori E, Ito JI, Adachi T, Takeda T, Sugahara K, Watanabe H, Saito K, Togashi H, Kawata S. Differentiation of bone marrow cells into cells that express liver-specific genes in vitro: implication of the Notch signals in differentiation. Biochem Biophys Res Commun, 2006, 304(4):691-5.
    90、 Fiegel HC, Lioznov MV, Cortes-Dericks L, Lange C, Kluth D, Fehse B, Zander AR. Liver-specific gene expression in cultured human hematopoietic stem cells. Stem Cells, 2003, 21(1) :98-104.
    91、 Yamazaki S, Miki K, Hasegawa K, Sata M, Takayama T, Makuuchi M. Sera from liver failure patients and a demethylating agent stimulate transdifferentiation of murine bone marrow cells into hepatocytes in coculture with nonparenchymal liver cells. JHepatol, 2003, 39(1): 17-23.
    92、 Ishikawa F, Drake CJ, Yang S, Fleming P, Minamiguchi H, Visconti RP, Crosby CV, Argraves WS, Harada M, Key LL Jr, Livingston AG, Wingard JR, Ogawa M. Transplanted human cord blood cells give rise to hepatocytes in engrafted mice. Ann N Y Acad Sci, 2003, 996:174-85.
    93、 Weng YS, Lin HY, Hsiang YJ, Hsieh CT, Li WT. The effects of different growth factors on human bone marrow stromal cells differentiating into hepatocyte-like cells. Adv Exp Med Biol, 2005, 534:119-28.
    94、Yamamoto N,Terai S,Ohata S,Watanabe T,Omori K,Shinoda K,Miyamoto K,Katada T,Sakaida I,Nishina H,Okita K.A subpopulation of bone marrow cells depleted by a novel antibody,anti-Liv8,is useful for cell therapy to repair damaged liver.Biochem Biophys Res Commun,2004,313(4):1110-8.
    95、Zhang CC,Lodish HF.Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells.Blood,2004,103(7):2513-21.
    96、Craig CE,Quaglia A,Selden C,howdell M,Hodgson H,Dhillon AP.The histopathology of regeneration in massive hepatic necrosis.Semin Liver Dis,2004,24(1):49-64.
    97、Petersen BE,Bowen WC,Patrene KD,et al.Bone marrow as a potential source of hepatic oval cells.Science,1999,284(5417):1168-1170.
    98、Theise ND,Badve S,Saxena R,et al.Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation.Hepatology,2000,31:235-240.
    99、Alison MR,Poulsom R,Jeffery R,et al.Hepatocytes from nonhepatic adult stem cells.Nature,2000,406:257.
    100 Theise ND,Nimmakayalu M,Gardner R,et al.Liver from bone marrow in humans.Hepatology,2000,32(1):11-16
    101、Oyagi S,Hirose M,Kojima M,Okuyama M,Kawase M,Nakamura T,Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CCl4-in jured rats.J Hepatol.2006,Arp;44(4):742-748.
    102 唐力军,高毅,姜晓丹,柳晓秋等人,人骨髓来源的多能成体祖细胞分离纯化的实验研究。中华神经医学杂志,2004年11月第3卷6期:422-424.
    103、唐力军,高毅,李浩,单毓强等,人骨髓来源的多能成体祖细胞分离纯化及体外培养的实验研究.中国临床康复,2005年,第9卷2期:85-87.
    104、唐力军,高毅,张志,李浩等,HFC,FGF-4体外定向诱导人骨髓来源的多能成体祖细胞向肝样细胞分化的特征性表形鉴定.解放军医学杂志,2004年第29卷11期:973-976.
    105、慕宁,汪艳,谢金敏,朱应乾等,免疫磁珠法分选人骨髓多能成体祖细胞及初步鉴定.第二军医大学学报,2006,27(10):1048-1051.
    106、慕宁,高毅,唐力军,双阴性选择法纯化培养人骨髓多能成体祖细胞.2005,25(5):535-537.
    107、唐力军,高毅,张志,李浩等,肝细胞生长因子联合成纤维细胞生长因子-4诱导人骨髓来源的多能成体祖细胞向肝样细胞得分化.2005,13(9):652-655.
    108、高毅,唐力军,慕宁,两种细胞因子诱导人骨髓来源的多能成体祖细胞向肝样细胞分化的作用.中华肝脏病杂志,2005,13(11):862-864.
    109、王海兰,高毅,蒋泽生,慕宁,人骨髓来源多能成体祖细胞ZHJ-MAPCs 与人肝细胞系Lo2体外共培养向肝样细胞得分化。世界华人消化杂志,2006,14(23):2294-2300.
    110、Kirschstein R,Lana R,Skirboll.Stem Cell:Scientific Progress and Future Research Direction.Report Prepared by The National Institutes of Health.2001
    111、Osawa M,Hanada K,Hamada H,et al.Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell.Science,1996,273:242-245
    112、Avital I,Inderbitzin D,Aoki T,et al.Isolation,characterization,and transplantation of bone marrow-derived hepatocyte stem cells.Biochem Biophys Res Commun,2001,288:156-164
    113、Lagasse E,Connors H,Al-Dhalimy M,et al.Purified hematopoietic stem cells can differentiate into hepatocytes in vivo.Nat Ned,2000,6:1229-1234
    114、 Lagasse E, Connors H, Al-Dhalimy M, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med, 2006, 6 (11): 1229-1234.
    115、 Pittenger MF, et al.Multilineage potential of adult human mesenchymal stem cell. Science, 1999, 284:143-147
    116、 Reyes M, roy Lund, Catherine M. Verfaile et al. Purification and ex vivo expansion of postnatal human marrow mesodermal rogenitor cells. Blood, 2005, 98: 2615-2625
    117、 Reyes M, Dudek A, Catherine M. Verfaillie, et al.Origin of endothelial progenitors in human post-natal bone marrow. J. Clin Invest, 2002, 109:37-346
    118、Robert E. Schwartz, Reyes M, Catherine M. Verfailie, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J. Clin. Invest, 2002, 109:291-1302.
    119、 Jiang YH, Balkrishna N. Jahagirdar, Catherine M. Verfailie, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002, 418(6893):41-49
    120、 Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 2002, 418 (6893): 41-49.
    121、Schwartz RE, Reyes M, Koodie L, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest, 2002, 109 (10): 1291-1302.
    122、Dabeva MD, PetkoV PM, Sandhu J, et al. Proliferation and differentiation of fetal liver epithelial progenitor cells after transplantation into adult rat liver, 2000, 156(6):2017-31.
    123、 Avital I, Feraresso C, Aoki T, et al. Bone marrow-derived liver stem cell and mature hepatocyte engraftment in livers undergoing rejection.
    Surgery,2002,132:384-90.
    
    124、Baumann U,Crosby HA,Ramani P,et al.Expression of the stemcell factor receptor c - kit in normal and diseased pediatric liver,identification of a human hepatic progenitor cell ?Hepatology,1999,30(1):112-117
    125、N ada A,TerriL,J lhn C et al.Expansion of transp lanted hepatocytes during liver regeneration.T ransp lantation,1997,64:5):816.
    126、Susumu E,Jacek R,L aura,T et al.Treatment of hypercho lestero lem ia in the watanabe rabbit using allogeneic hepatocellular transp lantation under a regeneration.T ransp lantation 1996,62(5):588.
    127、Ezio L,Ran O,Deb K et al.Long - term,near - to tal liverrep lacement by transp lantation of iso lated hepatocytes in rats treated w ith retro rsine.A m J p athol,1998,153(1):319.
    128、王少鑫,孙涛,骨髓干细胞移植诱导肝细胞再生的研究进展。中国医师进修杂志,2006年5月第29卷5期66-67。
    129、Roberto M.Lemoli,Lucia Catani,Simona Talarico,Elisabetta Loggi,Mobilization of Bone Marrow-Derived Hematopoietic and Endothelial Stem Cells After Orthotopic Liver Transplantation and Liver Resection.Stem Cells Vol.24 No.12 December 2006,pp.2817-2825
    130、Yasuo Y,H iromitsu H,Shinma Y et al.Recombinant humanhepatocyte trowth factor facilitates biliary transport after hepatocyte transplantation in eisai hyperbiliubinemic rats.D ig D isS ci,1997,42(30:522.
    131、Wang X,Willenbring H,Akkari Y,Torimaru Y,Foster M,Al-Dhalimy M,Lagasse E,Finegold M,Olson S,Grompe M.Cell fusion is the principal source of bone-marrow-derived hepatocytes.Nature,2003, 422(6934):897-901.
    
    132、Vassilopoulos G,Wang PR,Russell DW.Transplanted bone marrow regenerates liver by cell fusion.Nature,2003,422(6934):901-4.
    133、单毓强 硕士毕业论文“受体特异性骨髓干细胞诱导肝移植大鼠长期存活”。2004年7月。
    1)Starzl TE,MarchioroTL,Porter KA,etal,Factors determining short-and-long term survival after orthotropic liver homotransplantations the dog Surgery,1965,58:131-155
    2)Marc H,Dahlke,Felix C,Popp Nadine Eggent,Ludwig Hoy,et al,Differences in attitude toward living and post mortal liver donation in the United States Germany and Japan Psychosomatic 2005,46:58-64
    3)Strong RW,Lynch SV,Org TH,et al,Successful liver transplantation from a living donor to herson[J]N Eng J M ed,1990,322:1505
    4)范上达,王伟林,杨振帆,95例次肝移植临床分析 中国实用外科杂志1999年9月19卷9期,532-534
    5)Yamaka Y,Washita M,Honda K,et al,living liver transplantation using a right lobe graft from a living related donor.Transplantation 1994,57:1127-1130
    6)王学浩,李国强,活体肝移植的历史现状和发展前景 中华肝脏病杂志 2004,12卷6期 380-381
    7)Owen S,Sunman,Isao Fukunishi Tenure Allen and Martin Hertz liver organ donation:Social context,Clinical Encounter,and the Psychology of communication Psychosomatics 2005 46:1-6
    8)Dushyant S ahani,Roy D Souza,Rajagopai,Kadavigere et al,Evaluation of living liver transplant donor:method for precise anatomic definition by using a dedicated contrast-enhanced MR imaging protocol Radio Graphics 2004,24:957-967
    9)Zarrent Hermoye,Tsmel Laamari-Azjal,Zhujiang Cao,Zaurence Annet,et al,liver segmentation in living liver transplantation donors:comparison of semiautomatic and manual methods Radiology Jan 2005,234:171-178
    10)S Nadalin M Malago,C Valentin-Gamzo,G Testa HA Bata,C liuNR Fruhuaf,R Schaffer et ai,Preoperative donor liver biopsy for adult living donor liver transplantation: risks and benefits Liver Transpl 2005, ll(8):980-986
    11) Kiuchi T ,Kasahara M ,Uryuhara K ,et al .Impact of graft size mismatching on graft prognosis in liver transplantation from living donors . Transplantation 1999,67: 321-327
    12) Kawasaki S ,Makuuchi M ,Matsunami H ,et al .living related liver transplantation in adults Ann Surg 1998 227 :269-274
    13) Fan ST,Lo CM ,Liucl, Ying BH ,Chen JK ,NgIO safety of donors in living donor liver transplantation using right lobe grafts ,Arch 200 ,135 : 336-340
    14) Arianeb Mehrabi, Peter S chemmer, Jan Schmidt peter Sauer .Helmut Friess, et al, Heidelberg's first experiences in establishing a living-donation liver transplantation program Nephnol Dial Transplant. 2004,19 : 41-45
    15) Jc Coelho , MB Rarolin ,GA Baretta,SK Pimentel AC de Freitas and D Colman .Donor quality of life after living donor liver transplantation Arc Gastroenterology 2005,42(2)83-88
    16) AM Elola-Olaso ,EM Gonzalez ,Jc Diaz,I Garcia ,CL Segurala ,MA Usera ,et al .short-and long-term outcomes after living donor liver transplantation Transplant Proc 2005,37(9)3884-3886
    17) M Ben-Haim,M Carmiel,N Lubozky,R Keidar, P Katz et al ,Donor recruitment and selection for adult-to-adult living liver transplantation . Isr Med Assoc J 2005, 7(3): 169-173
    18) D Max Perkin ,MD Fred die ,Bray, J Farley and paola Piscine PhD, a global cancer statistics 2002 CA Cancer J Clin 2005 ,55 :74-108
    19) Y Sugawara and M Makuuchi living donor liver transplantation for patients with hepatitics C virus cirrhosis: Tokyo experience, Clin Gastroentenol Hepatic 2005, 3:122-124
    20) Inoue J ,Uero Y ,Kanno N ,Anzai H ,Kondo Y ,Moritoki Y ,Mikami E ,Chiba M ,et al, living related liver tranplantation for acute fulminante hepatitis B : experience from two possible hyper-acute cases . Tohoku J Exp Med 2005 205(2): 197-204
    21) Eddie R, Island MD,James Pomposelli,MD ,Elizabeth A ,Pomfret MD ,et al ,Twenty-year experience with liver transplantation for hepatocellular carcinoma Arch Surg 2005,140 :353-358.
    22) Lo CM ,Fan ST ,Liu CL, et al Extending the limit on the size of adult recipient in living donor liver transplantation using extend right lobe graft Transplantation 1997 ,27 :1524
    23) Such KS ,Yi NJ ,Kwon CH ,et al ,modified extended right hepatectomy focus on technical aspect Transplantation 2004,78(2):117
    24) M Kasahara ,Ytakada ,Y Fujimoto ,Y Ogura ,K ogawa ,et al ,impact of right lobe with middle hepatic vein graft in living donor liver transplantation .Am J Transplant 2005 ,5(6):1339-1346
    25) Mistsuo shimada MD ,PhD ,Sutoko shiotani MD ,Mizuki Ninomiya MD ,Takahivo Terashi MD ,et al .characteristic of liver graft in living donor adult liver transplantation : comparison between right-and-left-lobe graft. Arch Surg 2002,137:1174-1179
    26) S Grutta dauria ,L Mandala ,F Vasta ,D Cintonino ,A Musumeci, W Marsh,A Marcos .Improvement in hepatic parenchyma transaction for living related liver donor Transplant Proc 2005 ,37(6): 2589-2591
    27) Di Benedetto F, Medical devices and surquical technology week. Atlanta Feb 12, 2006 .520
    28) U Tannuri ,JG M aksoud-Filbo ,MM Silva L Suzuki ,MM Santos ,NE Giblli ,AA Ayoub et al .An alternative method of arterial reconstruction in pediatric living donor liver transplantation with the recipient right graftroepiploic artery Pediatric Transplant 2006 10(1) 101-104
    29) M Alper ,H Gundogan ,C Tokst and C O zek Microsurgical reconstruction of hepatic artery during living donor liver transplantation Microsurgery 2005 ,25(5) 378-383
    30) K Hasegawa Y Sugawara ,H Imamuna ,M Ikeda living donor liver transplantation for primary billiard cirrhosis retrospective analysis of patients in aisle center Transpl Int 2005 .18(7) 794-799
    31) 范上达, 任祖海 成人活体肝移植的现状和争议 J Clin Surg January 2005 vol 13 ,Nol ,8-9
    32) PF Middleton M Duffidd SV Lynth, RT Radbury, T House, P Stanon, D Verran living donor liver transplantation adult donor outcomes: a systematic review Liver Transpl 2006,12(1) 24-30
    33) Christopher R ,S hackleton MD, John M, Vierling MD, Nicholas Nissen MD, Paul Martin MD , et al Morbidity in living liver donors Arch Surg 2005 ,140 : 888-895
    34) Yoshihisa Kadama ,Yusnke, Sakuhara ,Paisuke Abo ,Tsuyoshi shimamura, et al Percutaneous transhumant angioplasty for hepatic artery stenosis after living donor liver transplantation Liver Transpl 2006 12(3) 465-469
    35) Toyomical Shabbat MD,Kyo,Itoh MD,Takeshi Kubo,MD ,Yogi Maetani MD et al,Percutaneous Tran hepatic billon dilation of portal venous steroid in patients with living
    donorliver transplantation Radiology 2005,235:1078-1083
    
    36)严律南,李波,曾勇,赵纪春等人 改进成人间活体肝移植的手术技术 中华器官移植杂志 2006 Vo27 No2:86-89
    37)Keiichi Kubota,Junji Kita,Mesuji shimoda,Kyu Rococo,Masato Kato et Intraoperative assessment of reconstructed vessels in living-donor liver transplantation,using a novel fluorescence imaging technique J hepatobiliary Pancreatic Surg 200613:100-104
    38)Sung-GYu Lee Techniques of reconstruction of hepatic veins in living-donor liver transplantation,especially for right hepatic vein and major short hepatic veins of right-lobe graft J hepatobiliary Pancreat Surg 2006 13:131-138
    39)Tomohide Hori,Taku Lida,Shintaro Yag,Kentaro Taniguchi,Chidur Yamamoto and Shako Mizuno et al KICG Value,a reliable real-time estimator of graft function accurately predicts outcomes in adult living-donor liver transplantation Liver Transplantation 2006 12:605-613.
    1、Marc H,Dahlke,Felix C,Popp Nadine Eggent,Ludwig Hoy,et al,Differences in attitude toward living and post mortal liver donation in the United States Germany and Japan Psychosomatic 2005,46:58-64
    2、Stanworth S J,Mewland AC.Stem cell:progress in research and edging towards the clinical setting. Clin Med, 2001, 1:378-382
    3、Goodell MA, Jackson KA, Majka SM, et al. Stem cell plasticity in muscle and bone marrow. Ann NY Acad Sci, 2001, 938:208-218
    4、Oscar K. Lee, Tom K. Kuo, Wei-Ming Chen, Kuan-Der Lee, Shie-Liang Hsieh, and Tain-Hsiung Chen, Isolation of multipotent mesenchymal stem cells from umbilical cord blood Blood 1 March2004,Vol 103, No 5: 1669-1675.
    5、Berna G, Leon-Quinto T, Ensenat-Waser R, et al. Stem cells and diabetes. Biomed Pharmacother, 2001, 55:206-212
    6、Rao MS, Mattson MP. Stem cells and aging: expanding the possibilities. Mech Aging Dev, 2001, 122:713-734.
    7、Roberto M. Lemoli, Lucia Catani, Simona Talarico, Elisabetta,et al, Mobilization of Bone Marrow-Derived Hematopoietic and Endothelial Stem Cells After Orthotopic Liver Transplantation and Liver Resection Stem Cells Vol. 24 No. 12 December 2006, pp. 2817-2825.
    8、 Günter Fürst, Jan Schulte am Esch, Ludger W. Poll, Stefan B. Hosch, L. Benjamin Fritz,et al, Portal Vein Embolization and Autologous CD133+ Bone Marrow Stem Cells for Liver Regeneration: Initial Experience Radiology 2007, 10.1148
    9、 Anuradha Menthenaa, Niloyjyoti Debb, Michael Oertela, Petar N. Grozdanova , et al ,Bone Marrow Progenitors Are Not the Source of Expanding Oval Cells in Injured Liver Stem Cells 2004;22:1049-1061
    10、Muriel Sudres, Francoise Norolf, Aurelie Trenado, Sylvie Gregoire,et al, Bone Marrow Mesenchymal Stem Cells Suppress Lymphocyte Proliferation In Vitro but Fail to Prevent Graft-versus-Host Disease in Micel The Journal of Immunology, 2006, 176: 7761-7767
    11、Shuji Teraia, Tsuyoshi Ishikawaa, Kaoru Omoria, Koji Aoyamaa, Yoshio Marumoto,etal, Improved Liver Function in Patients with Liver Cirrhosis After Autologous Bone Marrow Cell Infusion Therapy Stem Cells Vol. 24 No. 10 October 2006, pp. 2292-2298
    12、Min AD, Theise ND.Prospects for cell-based therapies for liver disease. Panminerva Med. 2004 Mar, 46(l):43-8.
    13、 中国医师进修杂志2006年第29卷第5期内科版 Chin J Postgrad Med ,May 2006 ,Vol. 29 No. 5A
    14、 Petersen BE , Bowen WC , Patrene KD , et alv.Bone marrow as a potential source of hepatic oval cells. Science, 1999,284 (5421) :1168-1170.
    15、 Reyes M, roy Lund, Catherine M.Verfaile et al.Purification and ex vivo expansion of postnatal human marrow mesodermal rogenitor cells. Blood, 2001, 98: 2615-2625
    16、 Reyes M, Dudek A, Catherine M.Verfaillie, et al.Origin of endothelial progenitors in human post-natal bone marrow. J.Clin Invest, 2002, 109:37-346
    17、 Robert E. Schwartz, Reyes M, Catherine M.Verfailie, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J. Clin. Invest, 2002, 109:291-1302.
    18、 Jiang YH, Balkrishna N. Jahagirdar, Catherine M.Verfailie,et al. Pluripotency of mesenchymal stem cells derived from adult manrow.Nature. 2002,418(6893):41-49
    19、 Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 2002, 418 (6893): 41-49.
    20、 Schwartz RE, Reyes M, Koodie L, et al. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest, 2002,109 (10): 1291-1302.
    21、 Theise ND , Badve S , Saxena R , et al. Derivation of hepatocy tesfrom bone marrow cells in mice after radiation - induced myeloablationv.Hepatology, 2000, 31 (1):235-240.
    22、 Heather AC , Crosby, Deirdre A , et al. Human hepatic stem - like cell isolated using c - kit or CD34 can differentiate into biliary epithet-lium.Gastroenterology, 2001,20(2):534-544.
    23、Oyagi S,Hirose M,Kojima M,Okuyama M,Kawase M,Nakamura T,Therapeutic effect of transplanting HGF-treated bone marrow mesenchymal cells into CC14-injured rats.J Hepatol.2006,Arp;44(4):742-748.
    24、唐力军,高毅,姜晓丹,柳晓秋等人,人骨髓来源的多能成体祖细胞分离纯化的实验研究。中华神经医学杂志,2004年11月第3卷6期:422-424.
    25、唐力军,高毅,李浩,单毓强等,人骨髓来源的多能成体祖细胞分离纯化及体外培养的实验研究.中国临床康复,2005年,第9卷2期:85-87.
    26、唐力军,高毅,张志,李浩等,HFG,FGF-4体外定向诱导人骨髓来源的多能成体祖细胞向肝样细胞分化的特征性表形鉴定.解放军医学杂志,2004年第29卷11期:973-976.
    27、慕宁,汪艳,谢金敏,朱应乾等,免疫磁珠法分选人骨髓多能成体祖细胞及初步鉴定.第二军医大学学报,2006,27(10):1048-1051.
    28、慕宁,高毅,唐力军,双阴性选择法纯化培养人骨髓多能成体祖细胞.2005,25(5):535-537.
    29、唐力军,高毅,张志,李浩等,肝细胞生长因子联合成纤维细胞生长因子-4诱导人骨髓来源的多能成体祖细胞向肝样细胞得分化.2005,13(9):652-655.
    30、高毅,唐力军,慕宁,两种细胞因子诱导人骨髓来源的多能成体祖细胞向肝样细胞分化的作用.中华肝脏病杂志,2005,13(11):862-864.
    31、王海兰,高毅,蒋泽生,慕宁,人骨髓来源多能成体祖细胞ZHJ-MAPCs 与人肝细胞系Lo2体外共培养向肝样细胞得分化。世界华人消化杂志,2006,14(23):2294-2300.
    32、N ada A,TerriL,J lhn C et al.Expansion of transplanted hepatocytes during liver regeneration.T ransp lantation,1997,64:5):816.
    33、Susumu E,Jacek R,L aura,T et al.T reatment ofhypercho lestero lem ia in the watanabe rabbit using allogeneic hepatocellular transplantation under a regeneration.T ransp lantation,1996,62(5):588.
    34、Ezio L,Ran O,Deb K et al.Long - term,near - to tal liverrep lacement by transp lantation of isolated hepatocytes in rats treated with retro rsine.A m Jp athol,
    1998,153(1):319.
    
    35、Vincent Donckier,Roberto Troisi,Michel Toungouz Isabelle Colic,Hans Van Vlierberghe,etal,Donor stem cell infusion after non-myeloablative conditioning for tolerance induction to HLA mismatched adult living-donor liver graft Transplant Immunology 13(2004):139-146
    36、Feng Liu,Xiaoben Pan,Guodong Chen,Dong Jiang,Xu Cong,Ran Fei,etal,Hematopoietic Stem Cells Mobilized by Granulocyte Colony-Stimulating Factor Partly Contribute to Liver Graft Regeneration After Partialo- rthotopic Liver Transplantation.Liver Transplantation,2006,12:1129-1137.
    37、王少鑫,孙涛,骨髓干细胞移植诱导肝细胞再生的研究进展。中国医师进修杂志,2006年5月第29卷5期:66-67
    38、Roberto M.Lemoli,Lucia Catani,Simona Talarico,Elisabetta Loggi,Mobilization of Bone Marrow-Derived Hematopoietic and Endothelial Stem Cells After Orthotopic Liver Transplantation and Liver Resection.Stem Cells Vol.24 No.12 December 2006,pp.2817-2825
    39、Yasuo Y,H iromitsu H,Shinma Y et al.Recombinant humanhepatocyte trow th facto r facilitates biliary transport after hepatocyte transplantation in eisai hyperbiliubinemic rats.D ig D isS ci,1997,42(30:522.
    40、George V.Mazariegosa,Alan F.Zahorchak,Jorge Reyes,Lynn Ostrowski,Bridget Flynn,Adriana Zeevib and Angus W.Thomson,Dendritic Cell Subset Ratio in Peripheral Blood Patients.American Journal of Transplantation 2003;3:689-696
    41、Ming Zhang,Quanxing Wang,Yushan Liu,Yanping Sun,Guoshan Ding Zhiren Fu,et al,Effective induction of immune tolerance by portal venous infusion with IL-10 gene-modified immature dendritic cells leading to prolongation of allograft survival.J Mol Med(2004)82:240-249
    42、Fred Fandrich,Bettina Dresske,Michael Bader,Maren Schulze,Embryonic stem cells share immune-privileged features relevant for tolerance induction.J Mol Med(2002)80:343-350
    
    43、James M,Mathewa,Rolando O,Garcia-Moralesa,Manuel Carrenoa,Yide Jin,Laphalle Fuller,Bonnie Blomberg,et al,Immune responses and their regulation by donor bone marrow cells in clinical organ transplantation.Transplant Immunology 11(2003)307-321
    44、James A,Martin,Yazan Duwayri,Gilbert Falcon,etal,Impact of Aging on Rat Bone Marrow-Derived Stem Cell Chondrogenesis.Biological Sciences and Medical Sciences,2007,62:136-148
    45、Quanjun Cui,Zengming Xiao,Xudong Li,Khaled J.Saleh,et al,Use of Genetically Engineered Bone-Marrow Stem Cells to Treat Femoral Defects:An Experimental Study,The Journal of Bone and Joint Surgery(American).2006,88:167-172.
    46、廖彩仙,张晓东,植一丹,应用自体骨髓肝内移植治疗肝硬化的实验研究。中华医学研究杂志,2004,4:215.
    47、吴理茂,李连达,刘红,宁可永等,自体骨髓干细胞移植与归远方联用治疗急慢性肝损伤实验研究,中国工程科学,2004,6:34-42.
    48、朱晓玲,时冰,李艳等人,自体骨髓干细胞肝移植1例,世界华人消化杂志,2006,14(2):242-243.
    49、Ciancio G,Burke GW,Moon J,Garcia-Morales R,RosenA,etal,Donor bone marrow infusion in deceased and living donor renal transplantation.Yonsei Medical Journal 2004,45(6):998-1003.
    50、Susumu Ikehara Intra-bone Marrow-Bone Marrow Transplantation:A New Strategy for Treatment of Stem Cell Disorders.Ann.N.Y.Acad.Sci.2005,1051:626-634.
    51、Xinyang Hu,Jianan Wang,Jie Chen,Ronghua Luo,etal Optimal temporal delivery of bone marrow mesenchymal stem cells in rats with myocardial infarction.Eur J Cardiothorac Surg 2007,31:438-443.
    52、Takashi Yazawa,Tetsuya Mizutani,Kazuya Yamada,Hiroko Kawata,etal, Differentiation of Adult Stem Cells Derived from Bone Marrow Stroma into Leydig or Adrenocortical Cells.Endocrinology, 2006, Vol. 147, No.9 .4104-4111.
    53、Vincent Donckier, Roberto Troisi, Michel Toungouz Isabelle Colle,Hans Van Vlierberghe, etal, Donor stem cell infusion after non-myeloablative conditioning for tolerance induction to HLA mismatched adult living-donor liver graft Transplant Immunology 13 (2004) 139- 146.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700