肝卵圆细胞移植治疗肝纤维化与肝功能不全的实验研究
|
摘要
目的：建立一种稳定而确实可靠的肝卵圆细胞分离方法,为后续的实验研究奠定基础。
方法：参照Bryon等的报道,利用携带GFP(绿色荧光蛋白)转基因C57BL/6小鼠12只,2只作为空白对照,10只喂以含浓度为0.1%的3,5-二乙酯基-1,4二氢三甲基毗啶(DDC),刺激卵圆细胞的增生。而后利用两步酶灌注法分离出肝非实质细胞,以Sca-1抗体标记的免疫磁珠分选方法加以纯化分离出携带有GFP的SCa-1+细胞。
结果：DDC喂养小鼠6周后,病理切片结果显示肝组织内可见明显的肝卵圆细胞增生反应。分离每只小鼠得可到约106/ml的非肝实质细胞,培养扩增约5d后可见克隆样生长的卵圆细胞,通过Sca-1抗体标记的免疫磁珠分选提纯。电镜下细胞直径10-15μm,呈铺路石样排列,多角形,折光性强,核大,卵圆形,胞浆少,核仁明显。经过鉴定,分离得到的Sca-1+细胞符合卵园细胞的形态学表现,也表达胆管上皮的表面标记OV-6及肝细胞的表面标记AFP,分离纯度达95%以上。
结论：该方法稳定可靠,可为肝卵圆细胞的相关研究提供较为理想的研究手段。
目的：研究肝卵圆细胞在治疗小鼠肝纤维化疾病中的有效性。
方法：SPF级C57BL/6小鼠利用皮下注射四氯化碳的方法,建立小鼠肝纤维化模型。40只肝纤维化模型小鼠分为两大组,将两大组小鼠根据是否继续皮下注射CCl4分为A、B两组,其中A组为施予处理后(HOCA或NSA),继续皮下注射CCl4,B组为施予处理后(HOCB或NSB),不再皮下注射CCl4,每小组10只小鼠。4周后观察肝功能各项指标、羟脯氨酸及胶原纤维及肝脏的病理改变,比较各组间的差别。
结果：卵圆细胞经脾脏移植后入肝,在共聚焦激光显微镜下可以观察到肝组织中存在GFP阳性细胞,这些细胞主要分布于门脉区。在A组继续皮下注射CCl4时,NSA组的ALT.AST均明显升高；而HOCA组ALT.AST明显降低,同时升高TP.ALB；HOCA组与NSA组两两比较,差异有统计学意义(P＜0.05)；在B组未继续皮下注射CCl4时,各组ALT.AST均下降,而且下降至近似正常水平,TP和ALB有升高,但两两比较,差异无统计学意义(P＞0.05)。肝脏病理学检测,在继续皮下注射CCl4情况下,治疗组肝纤维化程度有减轻,NSA组则呈典型肝纤维化改变；在未继续皮下注射CCl4情况下,两组肝纤维化程度都有不同程度减轻,HOCB组缓解更为明显。
结论：携带GFP的基因卵圆细胞经短暂体外培养扩增,经脾注射肝纤维化小鼠体内后,可定植于受者肝脏内(主要聚集于汇管区),并可缓解肝纤维化的进展,促进肝纤维化的逆转。
目的：比较肝卵圆细胞与骨髓间充质干细胞治疗小鼠肝纤维化的疗效差别。
方法：利用皮下注射四氯化碳的方法,建立小鼠肝纤维化模型。将肝纤维化/肝硬化成模小鼠60只随机分为6组,即HOC移植治疗组A (HOCA)、HOC移植治疗组B (HOCB), MSC移植治疗组A (MSCA)和MSC移植治疗组B (MSCB),对照组A(NSA)和对照组B(NSB),每组10只。根据不同的组别经脾分别输入卵圆细胞、生理盐水(NS)或四氯化碳。4周后观察肝功能各项指标、羟脯氨酸及胶原纤维及肝脏的病理改变,比较各组间的差别。
结果：SPF级C57BL/6小鼠85只,其中6只行骨髓间充质干细胞提取,79只行肝纤维化模型制作,成功造模64只(成功率81%)。分别对两组大鼠肝脏羟脯氨酸及胶原纤维含量这两项指标进行检测,统计分析发现两指标在各组间总体比较均有统计学差别(p＜0.05)。在继续皮下注射CCl4情况下,比较各组间差异显示HOCA组与MSCA组及NSA组之间的差异均有统计学意义(P＜0.05),而MSCA组与NSA组间无统计学意义(p>0.05)；在未继续皮下注射CCl4情况下,进一步比较各组间差异显示三组间均无统计学意义(p>0.05)。病理组织学检测结果,在未继续皮下注射CCl4情况下,各组肝纤维化程度都有不同程度减轻,肝纤维化程度HOC。组 结论：肝卵圆细胞和骨髓间充质干细胞经脾注射移植后,均能不同程度改善肝纤维化小鼠的肝功能,减轻其肝硬化的程度,但肝卵圆细胞的治疗效果更为明显。肝卵圆细胞移植可作为肝硬化疾病的一种新型的治疗方法进一步研究。
Objective:To establish a stable and reliable hepatic oval cells isolation method and build a solid foundation for the subsequent experiment research.
Methods:12 cases of the transgenic C57BL/6 mice, which were carried green fluorescent protein(GFP),10 of them were incorporated 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) in a standard food at a concentration of 0.1% to activate the oval cells proliferation,then the nonparenchymal cells in the liver were separated by in situ perfusion,finally we used Sca-1 antibody in conjunction with magnetic activated cell sorting (MACS) to separate the Sca-1+ cells.
Result:The pathological section shows conspicuous proliferative reactions in liver tissue after 6 weeks of DDC diet. We get 106/ml non nonparenchymal cells from each mouse.The cells have 10-15μm in diameter, cobblestones overlook, big nucleus, low endochylema under the electronic microscope. The results of identification prove that the Sca-1+ cells we separated had a morphology in accordance with hepatic oval cells, and expressed the surface markers of OV-6 and AFP.
Conclusion:The DDC diet protocol for mouse oval cells is reliable,and the MACS can be a efficient method to isolate the hepatic oval cells.
Objective:To investigate the feasibility of hepatic oval cells to treat cirrhosis in mice.
Methods:40 casese of SPF C57BL/6A mice were injected subcutaneously with CC14 to establish experimental liver cirrhosis model.Then the cirrhosis mice model were divided into two groups.The mice of one group were transplanted with the hepatic oval cells by spleen injection(HOC group),and the other one were injected with saline instead as a control group (NS group). At the meanwhile, the mice in each group were divided into two sub group, they were group of keeping injection of CCl4 (A group)and group of stopping CCl4 injection after transplantation(B group). Four weeks later, we investigate the liver function index, the hydroxyproline and collagen contents and the histopathological change among the groups to evaluate the effect of hepatic oval cells transplantation.
Result:It shows that the majority of hepatic oval cells, which were transplanted transpleen into the mice, were planted in the portal area under. The levels of ALT and AST were conspicuous higher in NSA group compared with that in HOCA (p<0.05). TP and ALB increased after transplantation but didn't show significance in statistics.The examination in pathology showed that cirrhosis relieved in HOCA group and got severe in NSA group.The results demonstrate that the function index and histopathological change were improved in the experimental group, especially in the group of ceasing CC14 injection after transplantation.
Conclusion:After transplanted into the liver by spleen injection, the hepatic oval cells could plant in the portal area, improve the liver fuction, and alleviate the cirrhosis level.
Objective:To compare the effectiveness of hepatic oval cells and bone marrow mesenchymal stem cells to treat cirrhosis in mice.
Methods:The mice were injected subcutaneously with CC14 to establish experimental liver cirrhosis.Then 60 cases of the cirrhosis mice were divided into three groups.The experimental was transplanted the hepatic oval cells by spleen injection(HOC), another group was transplanted with bone marrow mesenchymal stem cells(MSC), and the last group was injected saline instead as a blank control group(NS). In the while, the mice in each group were divided into two subset group, they were group of keeping injection of CCl4 (A group) and the group of stopping CCL4 injection (B group). Four weeks later, we investigate the liver function index, the hydroxyproline and collagen contents and the histopathological change among the groups to evaluate the effect of hepatic oval cells and bone marrow mesenchymal stem cells transplantation.
Result:85 cases the transgenic C57BL/6 mice,6 of them were sacrificed for bone marrow mesenchymal stem cells,79 of them were used for making cirrhosis mice model and succeeded in 64 cases (81%). After transplantation with hepatic oval cells and bone marrow mesenchymal stem cells, The hydroxyproline and collagen fibers in liver tissue were decrease in HOC group (p<0.05), The examination in pathology showed that liver cirrhosis level had improved in every A groups with different degree (HOCB Conclusion:The hepatic oval cells and bone marrow mesenchymal stem cells can both improve the liver fuction, and alleviate the cirrhosis level by transpleen transplantation, but the hepatic oval cells were even more effective. The hepatic oval cells transplant can be an effective method for cirrhosis disease treatment in mouse model.
方法：参照Bryon等的报道,利用携带GFP(绿色荧光蛋白)转基因C57BL/6小鼠12只,2只作为空白对照,10只喂以含浓度为0.1%的3,5-二乙酯基-1,4二氢三甲基毗啶(DDC),刺激卵圆细胞的增生。而后利用两步酶灌注法分离出肝非实质细胞,以Sca-1抗体标记的免疫磁珠分选方法加以纯化分离出携带有GFP的SCa-1+细胞。
结果：DDC喂养小鼠6周后,病理切片结果显示肝组织内可见明显的肝卵圆细胞增生反应。分离每只小鼠得可到约106/ml的非肝实质细胞,培养扩增约5d后可见克隆样生长的卵圆细胞,通过Sca-1抗体标记的免疫磁珠分选提纯。电镜下细胞直径10-15μm,呈铺路石样排列,多角形,折光性强,核大,卵圆形,胞浆少,核仁明显。经过鉴定,分离得到的Sca-1+细胞符合卵园细胞的形态学表现,也表达胆管上皮的表面标记OV-6及肝细胞的表面标记AFP,分离纯度达95%以上。
结论：该方法稳定可靠,可为肝卵圆细胞的相关研究提供较为理想的研究手段。
目的：研究肝卵圆细胞在治疗小鼠肝纤维化疾病中的有效性。
方法：SPF级C57BL/6小鼠利用皮下注射四氯化碳的方法,建立小鼠肝纤维化模型。40只肝纤维化模型小鼠分为两大组,将两大组小鼠根据是否继续皮下注射CCl4分为A、B两组,其中A组为施予处理后(HOCA或NSA),继续皮下注射CCl4,B组为施予处理后(HOCB或NSB),不再皮下注射CCl4,每小组10只小鼠。4周后观察肝功能各项指标、羟脯氨酸及胶原纤维及肝脏的病理改变,比较各组间的差别。
结果：卵圆细胞经脾脏移植后入肝,在共聚焦激光显微镜下可以观察到肝组织中存在GFP阳性细胞,这些细胞主要分布于门脉区。在A组继续皮下注射CCl4时,NSA组的ALT.AST均明显升高；而HOCA组ALT.AST明显降低,同时升高TP.ALB；HOCA组与NSA组两两比较,差异有统计学意义(P＜0.05)；在B组未继续皮下注射CCl4时,各组ALT.AST均下降,而且下降至近似正常水平,TP和ALB有升高,但两两比较,差异无统计学意义(P＞0.05)。肝脏病理学检测,在继续皮下注射CCl4情况下,治疗组肝纤维化程度有减轻,NSA组则呈典型肝纤维化改变；在未继续皮下注射CCl4情况下,两组肝纤维化程度都有不同程度减轻,HOCB组缓解更为明显。
结论：携带GFP的基因卵圆细胞经短暂体外培养扩增,经脾注射肝纤维化小鼠体内后,可定植于受者肝脏内(主要聚集于汇管区),并可缓解肝纤维化的进展,促进肝纤维化的逆转。
目的：比较肝卵圆细胞与骨髓间充质干细胞治疗小鼠肝纤维化的疗效差别。
方法：利用皮下注射四氯化碳的方法,建立小鼠肝纤维化模型。将肝纤维化/肝硬化成模小鼠60只随机分为6组,即HOC移植治疗组A (HOCA)、HOC移植治疗组B (HOCB), MSC移植治疗组A (MSCA)和MSC移植治疗组B (MSCB),对照组A(NSA)和对照组B(NSB),每组10只。根据不同的组别经脾分别输入卵圆细胞、生理盐水(NS)或四氯化碳。4周后观察肝功能各项指标、羟脯氨酸及胶原纤维及肝脏的病理改变,比较各组间的差别。
结果：SPF级C57BL/6小鼠85只,其中6只行骨髓间充质干细胞提取,79只行肝纤维化模型制作,成功造模64只(成功率81%)。分别对两组大鼠肝脏羟脯氨酸及胶原纤维含量这两项指标进行检测,统计分析发现两指标在各组间总体比较均有统计学差别(p＜0.05)。在继续皮下注射CCl4情况下,比较各组间差异显示HOCA组与MSCA组及NSA组之间的差异均有统计学意义(P＜0.05),而MSCA组与NSA组间无统计学意义(p>0.05)；在未继续皮下注射CCl4情况下,进一步比较各组间差异显示三组间均无统计学意义(p>0.05)。病理组织学检测结果,在未继续皮下注射CCl4情况下,各组肝纤维化程度都有不同程度减轻,肝纤维化程度HOC。组
Objective:To establish a stable and reliable hepatic oval cells isolation method and build a solid foundation for the subsequent experiment research.
Methods:12 cases of the transgenic C57BL/6 mice, which were carried green fluorescent protein(GFP),10 of them were incorporated 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) in a standard food at a concentration of 0.1% to activate the oval cells proliferation,then the nonparenchymal cells in the liver were separated by in situ perfusion,finally we used Sca-1 antibody in conjunction with magnetic activated cell sorting (MACS) to separate the Sca-1+ cells.
Result:The pathological section shows conspicuous proliferative reactions in liver tissue after 6 weeks of DDC diet. We get 106/ml non nonparenchymal cells from each mouse.The cells have 10-15μm in diameter, cobblestones overlook, big nucleus, low endochylema under the electronic microscope. The results of identification prove that the Sca-1+ cells we separated had a morphology in accordance with hepatic oval cells, and expressed the surface markers of OV-6 and AFP.
Conclusion:The DDC diet protocol for mouse oval cells is reliable,and the MACS can be a efficient method to isolate the hepatic oval cells.
Objective:To investigate the feasibility of hepatic oval cells to treat cirrhosis in mice.
Methods:40 casese of SPF C57BL/6A mice were injected subcutaneously with CC14 to establish experimental liver cirrhosis model.Then the cirrhosis mice model were divided into two groups.The mice of one group were transplanted with the hepatic oval cells by spleen injection(HOC group),and the other one were injected with saline instead as a control group (NS group). At the meanwhile, the mice in each group were divided into two sub group, they were group of keeping injection of CCl4 (A group)and group of stopping CCl4 injection after transplantation(B group). Four weeks later, we investigate the liver function index, the hydroxyproline and collagen contents and the histopathological change among the groups to evaluate the effect of hepatic oval cells transplantation.
Result:It shows that the majority of hepatic oval cells, which were transplanted transpleen into the mice, were planted in the portal area under. The levels of ALT and AST were conspicuous higher in NSA group compared with that in HOCA (p<0.05). TP and ALB increased after transplantation but didn't show significance in statistics.The examination in pathology showed that cirrhosis relieved in HOCA group and got severe in NSA group.The results demonstrate that the function index and histopathological change were improved in the experimental group, especially in the group of ceasing CC14 injection after transplantation.
Conclusion:After transplanted into the liver by spleen injection, the hepatic oval cells could plant in the portal area, improve the liver fuction, and alleviate the cirrhosis level.
Objective:To compare the effectiveness of hepatic oval cells and bone marrow mesenchymal stem cells to treat cirrhosis in mice.
Methods:The mice were injected subcutaneously with CC14 to establish experimental liver cirrhosis.Then 60 cases of the cirrhosis mice were divided into three groups.The experimental was transplanted the hepatic oval cells by spleen injection(HOC), another group was transplanted with bone marrow mesenchymal stem cells(MSC), and the last group was injected saline instead as a blank control group(NS). In the while, the mice in each group were divided into two subset group, they were group of keeping injection of CCl4 (A group) and the group of stopping CCL4 injection (B group). Four weeks later, we investigate the liver function index, the hydroxyproline and collagen contents and the histopathological change among the groups to evaluate the effect of hepatic oval cells and bone marrow mesenchymal stem cells transplantation.
Result:85 cases the transgenic C57BL/6 mice,6 of them were sacrificed for bone marrow mesenchymal stem cells,79 of them were used for making cirrhosis mice model and succeeded in 64 cases (81%). After transplantation with hepatic oval cells and bone marrow mesenchymal stem cells, The hydroxyproline and collagen fibers in liver tissue were decrease in HOC group (p<0.05), The examination in pathology showed that liver cirrhosis level had improved in every A groups with different degree (HOCB
引文
[1]高春芳,陆伦根主编,纤维化疾病的基础和临床。上海：上海科学技术出版社,2004,265-267。
[2]李才主编,器官纤维化基础与临床。北京：人民卫生出版社,2003,44-70。
[3]程明亮,杨长青主编,肝纤维化基础研究及临床。(第二版)北京：人民卫生出版社,2002,20-30。
[4]漆德芳主编, 肝硬化。 北京：北京科学技术出版社,2000,85-90。
[5]厉有名,中国酒精性肝病的研究现状。现代消化及介入诊疗,2007,12(4)：235-236.
[6]Refik Mas M, Comert B, Oncu K, et al. The effect of taurine treatment on oxidative stress in experimental liver fibrosis. Hepatol Res,2008,28(4):207-215.
[7]de Bleser PJ, Jannes P, van Buul-Offers SC, et al. Insulinlike growth factor-II/mannose 6-phosphate receptor is expressed on CC14-exposed rat fat-storing cells and facilitates activation of latent transforming growth factor-beta in cocultures with sinusoidal endothelial cells. Hepatology JT,1995,21(5):1429-1437.
[8]王宝恩,王泰龄,等.复方861对肝星状细胞增殖和凋亡的干预作用.中华肝脏病杂志,2000,8：78-80.
[9]Yao XX, Tang YW, Yao DM, et al. Effects of Yigan Decoction on proliferation and apoptosis of hepatic stellate cells. World J Gastroenterol,2002,8(3):511-514.
[10]Novobrantseva TI, Majeau GR, Amatucci A, et al. Attenuated liver fibrosis in the absence of B cells. J Clin Invest,2005,115(11):3072-3082.
[11]Bataller R, Brenner DA. Liver fibrosis. J Clin Invest JT-The Journal of clinical investigation,2005,115(2):209-218.
[12]Wright MC, Issa R, Smart DE, et al. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology,2001,121(3):685-698.
[13]梁扩寰.肝脏病学[M].北京：人民卫生出版社,1995.234-235.
[14]华海婴,郭旭光,杨波,肝纤维化的治疗和展望。医药导报,2007,26(4) 405-407。
[15]晁岚,张慧琴等,人胚胎干细胞的研究进展。现代妇产科进展,2003,12(4)：293-297
[16]Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature JT-Nature,2008,418(6893):41-49.
[17]Ortiz LA, Gambelli F, McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A,2003,100(14):8407-8411.
[18]Sakaida I, Terai S, Yamamoto N, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology,2008,40(6):1304-1311.
[19]Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med, 2003,9(9):1195-1201.
[20]Zhao DC, Lei JX, Chen R, et al. Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol, 2005,11(22):3431-3440.
[21]Carvalho AB, Quintanilha LF, Dias JV, Paredes BD, Mannheimer EG. Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury. Stem Cells.2008,26(5): 1307-1314
[22]Quintanilha LF, Mannheimer EG, Carvalho AB, Paredes BD, Dias JV. Bone marrow cell transplant does not prevent or reverse murine liver cirrhosis. Cell Transplant.2008;17(8):943-953
[23]Malhi H, Gupta S. Hepatocyte transplantation:new horizons and challenges. J Hepatobiliary Pancreat Surg 2001,8(1):40-50.
[24]Shiojiri N, Lemire JM, Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Res 1991;51:2611-2620.
[25]Shiojiri N. The origin of intrahepatic bile duct cells in the mouse. J Embryol Exp Morphol 1984;79:25-39.
[26]Alison MR. Liver stem cells:implications for hepatocarcinogenesis. Stem Cell Rev.2005;1(3):253-260
[27]Ln Guo-yue, Zhang Ping, Li Hong, Li Shuang, Wang Guang-yi et al. Isolation, culture and identification of adult hepatic stem cells in vitro. Journal of Clinical Rehabilitative Tissue Engineering Research 2007;50:10169-10172
[28]Abelev Gl. Eraiser TL. Cellular aspeccts of alpha-fetoprotein re-expression in tumors. Semin Cancer Biol 1999:9(2):95 - 107
[29]Ishikawa K. Sasaki A, Haraguchi N,et al. A case of an alpha-fetoprotein-producing intrahepatic cholangiocarcinoma suggests probable cancer stem cell origin. Omcologist 2007:12(3):320-324
[30]Sell S, Osborn K, Leffert HL. Autoradiography of "oval cells" appearing rapidly in the livers of rats fed N-2-fluorenylacetamide in a choline devoid diet. Carcinogenesis 1981;2:7-14.
[31]Sell S, Salman J. Light-and electron-microscopic autoradiographic analysis of proliferating cells during the early stages of chemical hepatocarcinogenesis in the rat induced by feeding N-2-fluorenylacetamide in a choline-deficient diet. Am J Pathol 1984; 114:287-300.
[32]Evarts RP, Nagy P, Nakatsukasa H, Marsden E, Thorgeirsson SS. In vivo differentiation of rat liver oval cells into hepatocytes. Cancer Res 1989;49:1541-1547.
[33]Novikoff PM, Yam A, Oikawa I.Blast-like cell compartment in carcinogen-induced proliferating bile ductules. Am J Pathol 1996; 148:1473-1492.
[34]Bisgaard HC, Nagy P, Santoni-Rugiu E, Thorgeirsson SS.Proliferation, apoptosis, and induction of hepatic transcription factors are characteristics of the early response of biliary epithelial (oval) cells to chemical carcinogens. Hepatology 1996;23:62-70.
[35]Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature,2000,406(6793):257.
[36]Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans. Hepatology,2000,32(1):11-16.
[37]Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science 1999;284:1168-1170.
[38]Bryon E. Petersen, Brian Grossbard, et al. Mouse A6-Positive Hepatic Oval Cells Also Express Several Hematopoietic Stem Cell Markers. Hepatology,2003,37(3): 632-640.
[39]Gordon GJ. Butz GM, Grisham JW, et al.Isolation, short-term culture, and transplantatiOn of small hepatocyte-like progenitor cells from retrosisine. exposed rats. Tmnsplantation 2002; 73(8):1236-1243
[40]Suzuki A、Zheng Y w. Kondo R et al. Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver。Hepatology。 2000; 32(6):1230-1239
[41]Lv Guo-yue, Zhang Ping, Li Hong, Li Shuang, Wang Guang-yi et al. Isolation, culture and identification of adult hepatic stem cells in vitro. Journal of Clinical Rehabilitative Tissue Engineering Research 2007;50:10169-10172
[42]居胜红,滕皋军,陆海华等,大鼠间充质干细胞超顺磁性氧化铁标记和经脾移植后的MR示踪研究。中华放射学杂志,2006,40(2)：127-132.
[43]Suzuki A、Zheng Y w. Kondo R et al. Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver。 Hepatology。 2000; 32(6):1230.1239
[44]Seglen PO. Prenparation of isolated rat live cells. Methods Cell Biol1976; 13: 29-83
[45]Avital I, lnderbizin D. Aoki et al isolation, characte rization, and transDlantation of bone marrow-derived hepatocyte stem cells Biochem Biophys Res Commun 2001; 288(11):156-166
[46]Gordon GJ. Butz GM, Grisham JW, et al.Isolation, short-term culture, and transplantatiOn of small hepatocyte-like progenitor cells from retrosisine. exposed rats. Tmnsplantation 2002; 73(8):1236-1243
[47]Taniguchi H. Suzuki A, Zheng et al. Usefulness of flow cytometric cell sorting for enrichment of hepatic stem and progenitor cells in the liver. Transpiant Proc 2000; 32(21:249-251
[48]Lv Guo-yue, Zhang Ping, Li Hong, Li Shuang, Wang Guang-yi et al. Isolation, culture and identification of adult hepatic stem cells in vitro. Journal of Clinical Rehabilitative Tissue Engineering Research 2007;50:10169-10172
[49]Faris RA,Konkin T,Halpert G.Liver stem cells:apotential source of hepatocytes for the treatment of human liver disease.Artifi Organs,2001,25(7):513-521
[50]Matsusaka S,Toyosaka A,Nakasho K,et al.The role of oval cells in rats hepatocyte transplantation. Transplantation,2000,70(3):441-446
[51]Yasui O, Miura N, Terada K, et al.Isolation of oval cells from long-evans cinnamon rats and their transplantation into hepatocytes in vivo in the rat liver.Hepatology,1997,25(2):329-334
[52]杜智,李涛,张金卷,朱争艳等,肝干细胞移植治疗大鼠爆发性肝功能衰竭的实验研究。生物医学工程与临床,2006 10(6)：346-349
[53]Monga SP, Tang Y, Candotti F,et al.Expansion of hepatic and hematopoietic stemcells utilizing mouse embryonic liver explants. Cell Transplant,2001,10 (1):81-89.
[54]Strom S C, Fisher R A, Thompson M T, et al. Hepatocyte transplantation as a bridge to ortho-topic liver transplantation in terminal liver faliure. Transplantation, 1997,63:559-567
[55]Emerson RW. Human hepatocyte transplantation:gene therapy and more? Pediatrics,1998,102:647-659
[56]ArkadopoulosN, LiljaH, SuhKS, etal. Introsplenic transplantation of allogenic hepatocytes pro-longs survival in anhepatic trts. Hepatology,1998,28:1365-1376
[57]Chatterjee S, Vrolix G, Depoortere I, Peeters T, Van Marck E. The therapeutic effect of the neuropeptide hormone somatostatin on Schistosoma mansoni caused liver fibrosis. BMC Infect Dis 2005; 5:45
[58]Sato R, Maesawa C, Fujisawa K, Wada K, Oikawa K, Takikawa Y, Suzuki K, Oikawa H, Ishikawa K, Masuda T. Prevention of critical telomere shorten-ing by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis. Gut 2004; 53:1001-1009
[59]Liu QH, Li DG, Huang X, Zong CH, Xu QF, Lu HM. Suppressive effects of 17beta-estradiol on hepatic fibrosis in CC14-induced rat model. World J Gastroenterol 2004; 10:1315-1320
[60]Shi MX, Fang BJ, Liao LM, Yang SG, Liu YH, Zhao CH. Flkl+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Shengwu Gongcheng Xuebao 2005; 21:396-401
[61]Kang JS, Wanibuchi H, Morimura K, Puatanachok-chai R, Salim El, Hagihara A, Seki S, Fukushima S. Enhancement by estradiol 3-benzoate in thioaceta-mide-induced liver cirrhosis of rats. Toxicol Sci 2005; 85:720-726
[62]Hata J, Ikeda E, Uno H, Asano S. Expression of hepatocyte growth factor mRNA in rat liver cirrhosis induced by N-nitrosodimethylamine as evidenced by in situ RT-PCR. J Histochem Cytochem 2002; 50:1461-1468
[63]Sakaida I, Hironaka K, Terai S, Okita K. Gadolinium chloride reverses dimethylnitrosamine (DMN)-induced rat liver fibrosis with increased matrix metalloproteinases (MMPs) of Kupffer cells. Life Sci 2003; 72:943-959
[64]Brond L, Hadrup N, Salling N, Torp M, Graebe M, Christensen S, Nielsen S, Jonassen TE. Uncoupling of vasopressin signaling in collecting ducts from rats with CBL-induced liver cirrhosis. Am J Physiol Renal Physiol 2004; 287:F806-F815
[65]Li J, Niu JZ, Wang JF, Li Y, Tao XH. Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model. World J Gastroenterol 2005; 11:6483-6488
[66]Zhao DC, Lei JX, Chen R, et al. Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol, 2005,11(22):3431-3440.
[67]Gao J, Dennis JE, Muzic RF, et al. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs,2001, 169(1):12-20.
[68]Naughton MA, Walport MJ, Wurzner R, et al. Organ-specific contribution to circulating C7 levels by the bone marrow and liver in humans. Eur J Immunol, 1996,26(9):2108-2112.
[69]Alison MR, Poulsom R, Forbes SJ. Update on hepatic stem cells. Liver, 2001,21(6):367-373.
[70]Avital I, Inderbitzin D, Aoki T, et al. Isolation, characterization, and transplant- tation of bone marrow-derived hepatocyte stem cells. Biochem Biophys Res Commun, 2001,288(1):156-164.
[71]Brill S, Holst P, Sigal S, et al. Hepatic progenitor populations in embryonic, neonatal, and adult liver. Proc Soc Exp Biol Med,1993,204(3):261-269.
[72]Braun KM, Sandgren EP. Cellular origin of regenerating parenchyma in a mouse model of severe hepatic injury.Am J Pathol,2000,157(2):561-569.
[73]Petersen BE. Hepatic "stem"cells:coming full circle. Blood cells Mol Dis,2001,27(3):590-600.
[74]Ohashi K,Park F,Kay MA.Hepatocyte transplantation:clinical and experimental application J Mol Med,2001,79(11):617-630.
[1]Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science JT-Science,1998,282(5391):1145-1147.
[2]Boiani M, Eckardt S, Scholer HR, et al. Oct4 distribution and level in mouse clones:consequences for pluripotency. Genes Dev JT-Genes & development, 2002,16(10):1209-1219.
[3]Suemori H, Tada T, Torii R, et al. Establishment of embryonic stem cell lines from cynomolgus monkey blastocysts produced by IVF or ICSI. Dev Dyn JT Developmental dynamics:an official publication of the American Association of Anatomists,2001,222(2):273-279.
[4]Jackson KA, Mi T, Goodell MA. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America,1999,96(25): 14482-14486.
[5]Almeida-Porada G, Porada C, Zanjani ED. Adult stem cell plasticity and methods of detection. Rev Clin Exp Hematol JT-Reviews in clinical and experimental hematology,2001,5(1):26-41.
[6]Forbes SJ, Vig P, Poulsom R, et al. Adult stem cell plasticity:new pathways of tissue regeneration become visible. Clin Sci (Lond) JT-Clinical science (London, England:1979),2002,103(4):355-369.
[7]Slack JM. Stem cells in epithelial tissues. Science JT-Science,2000,287(5457): 1431-3.
[8]Tropepe V, Coles BL, Chiasson BJ, et al. Retinal stem cells in the adult mammalian eye. Science JT-Science,2000,287(5460):2032-2036.
[9]van der Kooy D, Weiss S. Why stem cells?. Science JT-Science,2000,287(5457): 1439-1441.
[10]Loeffler M, Roeder I. Tissue stem cells:definition, plasticity, heterogeneity, self-organization and models-a conceptual approach. Cells Tissues Organs JT-Cells, tissues, organs,2002,171(1):8-26.
[11]Coulombel L. [Adult tissue stem cells:definition, identification and therapeutic use]. Journ Annu Diabetol Hotel Dieu JT-Journees annuelles de diabetologie de 1'Hotel-Dieu,2003:1-16.
[12]Parker GC, Anastassova-Kristeva M, Eisenberg LM, et.al. Stem cells:shibboleths of development, part Ⅱ:Toward a functional definition. Stem Cells Dev JT-Stem cells and development,2005,14(5):463-469.
[13]Burgin MT, Burkli P. [Embryos and embryo-like entities:problem of definition in the draft of the Swiss embryonic research law]. Ther Umsch JT-Therapeutische Umschau. Revue therapeutique,2002,59(11):613-617.
[14]Okano H. [Identification of neural stem cells in adult human brain:its implication in the strategy for repairing the damaged central nervous system]. Rinsho Shinkeigaku JT-Rinsh inverted question mark shinkeigaku= Clinical neurology,2005,45(11): 871-873.
[15]Bianchi de Di Risio CC, Callero F, Hidalgo A, et al.[Mesenchymal stem cells.Differentiation and alternative source of neural tissue]. Medicina (B Aires) JT-Medicina,2004,64(6):543-549.
[16]Chertkov IL, Drize NI. ["Plasticity" of bone marrow stem cells]. Ter Arkh JT-Terapevticheskii arkhiv,2004,76(7):5-11.
[17]Weissman IL. Medicine:politic stem cells. Nature JT-Nature,2006,439 (7073):145-7.
[18]Weissman IL. Stem cells:units of development, units of regeneration, and units in evolution. Cell JT-Cell,2000,100(1):157-168.
[19]Stevens D. Embryonic stem cell research:will President Bush's limitation on federal funding put the United States at a disadvantage? A comparison between U.S. and international law. Houst J Int Law JT-Houston journal of international law, 2003,25(3):623-653.
[20]Cotsarelis G, Kaur P, Dhouailly D, et al. Epithelial stem cells in the skin: definition, markers, localization and functions. Exp Dermatol JT-Experimental dermatology,1999,8(1):80-68.
[21]Li A, Simmons PJ, Kaur P. Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America, 1998,95(7):3902-3907.
[22]Tuoya, Hirayama K, Nagaoka T, et al. Identification of cell surface marker candidates on SV-T2 cells using DNA microarray on DLC-coated glass. Biochem Biophys Res Commun JT-Biochemical and biophysical research communications, 2005,334(1):263-268.
[23]David R, Groebner M, Franz WM. Magnetic cell sorting purification of differentiated embryonic stem cells stably expressing truncated human CD4 as surface marker. Stem Cells JT-Stem cells (Dayton, Ohio),2005,23(4):477-482.
[24]Stamp L, Crosby HA, Hawes SM, et al. A novel cell-surface marker found on human embryonic hepatoblasts and a subpopulation of hepatic biliary epithelial cells. Stem Cells JT-Stem cells (Dayton, Ohio),2005,23(1):103-112.
[25]Ko IK, Kato K, Iwata H. Antibody microarray for correlating cell phenotype with surface marker. Biomaterials JT-Biomaterials,2005,26(6):687-696.
[26]Fukada S, Higuchi S, Segawa M, et al. Purification and cell-surface marker characterization of quiescent satellite cells from murine skeletal muscle by a novel monoclonal antibody. Exp Cell Res JT-Experimental cell research,2004,296(2): 245-255.
[27]Kang EM, Zickler PP, Burns S, et al. Hematopoietic stem cell transplantation prevents diabetes in NOD mice but does not contribute to significant islet cell regeneration once disease is established. Exp Hematol JT-Experimental hematology, 2005,33(6):699-705.
[28]Singh Roy N, Nakano T, Xuing L, et al. Enhancer-specified GFP-based FACS purification of human spinal motor neurons from embryonic stem cells. Exp Neurol JT-Experimental neurology,2005,196(2):224-234.
[29]Fujimura J, Ogawa R, Mizuno H, et al. Neural differentiation of adipose-derived stem cells isolated from GFP transgenic mice. Biochem Biophys Res Commun JT-Biochemical and biophysical research communications,2005,333(1):116-121.
[30]Xia Z, Ye H, Locklin RM, et al. Efficient characterisation of human cell-bioceramic interactions in vitro and in vivo by using enhanced GFP-labelled mesenchymal stem cells. Biomaterials JT-Biomaterials,2005,26(29):5790-5800.
[31]Morgan DO.Principles of CDK regulation.Nature JT-Nature,1995,374(6518): 131-134.
[32]Ohshima T, Gilmore EC, Longenecker G, et al. Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous. J Neurosci JT-The Journal of neuroscience:the official journal of the Society for Neuroscience,1999,19(14): 6017-6026.
[33]Sondhi SM, Singh N, Kumar A, et al. Synthesis, anti-inflammatory, analgesic and kinase (CDK-1, CDK-5 and GSK-3) inhibition activity evaluation of benzimidazole/ benzoxazole derivatives and some Schiff s bases. Bioorg Med Chem,2006.
[34]Uziel T, Zindy F, Sherr CJ, et al. The CDK Inhibitor pl8(Ink4c) is a Tumor Suppressor in Medulloblastoma. Cell Cycle,2006,5(4).
[35]Dai Y, Hamm TE, Dent P, et al. Cyclin D1 Overexpression Increases the Susceptibility of Human U266 Myeloma Cells to CDK Inhibitors Through a Process Involving p130-, p107-and E2F-Dependent S Phase Entry. Cell Cycle,2006,5(4).
[36]Zannoni GF, Faraglia B, Tarquini E, et al. Expression of the CDK inhibitor p27(kip1) and oxidative DNA damage in non-neoplastic and neoplastic vulvar epithelial lesions. Mod Pathol,2006.
[37]Chou HY, Chou HT, Lee SC. Cdk-dependent activation of poly(ADP-ribose) polymerase member 10 (PARP10). J Biol Chem,2006.
[38]Coleman ML, Densham RM, Croft DR, et al. Stability of p21(Wafl/Cipl) CDK inhibitor protein is responsive to RhoA-mediated regulation of the actin cytoskeleton. Oncogene,2006.
[39]Pang L, Reddy PV, McAuliffe CI, et al. Studies on BrdU labeling of hematopoietic cells:stem cells and cell lines. J Cell Physiol JT-Journal of cellular physiology,2003,197(2):251-260.
[40]Van Bockstaele DR, Lardon F, Snoeck HW, et al. BrdU-Hoechst-ethidium bromide (EB) quenching technique for studying kinetics of hematopoiesis. Blood JT- Blood,1992,80(1):289-291.
[41]Pietrzyk ME, Priestley GV, Wolf NS. Normal cycling patterns of hematopoietic stem cell subpopulations:an assay using long-term in vivo BrdU infusion. Blood JT Blood,1985,66(6):1460-1462.
[42]Oostendorp RA, Audet J, Eaves CJ. High-resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro and in vivo. Blood JT-Blood,2000,95(3):855-862.
[43]Shaaban AF, Kim HB, Milner R, et al. A kinetic model for the homing and migration of prenatally transplanted marrow. Blood JT-Blood,1999,94(9): 3251-3257.
[44]Flake AW, Zanjani ED. In utero hematopoietic stem cell transplantation: ontogenic opportunities and biologic barriers. Blood JT-Blood,1999,94(7): 2179-2191.
[45]Caldwell MC, Datta S. Expression of cyclin E or DP/E2F rescues the G1 arrest of trol mutant neuroblasts in the Drosophila larval central nervous system. Mech Dev JT-Mechanisms of development,1998,79(1-2):121-130.
[46]Ghiani CA, Yuan X, Eisen AM, et al. Voltage-activated K+ channels and membrane depolarization regulate accumulation of the cyclin-dependent kinase inhibitors p27(Kipl) and p21(CIP1) in glial progenitor cells. J Neurosci JT-The Journal of neuroscience:the official journal of the Society for Neuroscience, 1999,19(13):5380-5392.
[47]Ghiani CA, Eisen AM, Yuan X, et al. Neurotransmitter receptor activation triggers p27(Kip1)and p21(CIP1) accumulation and G1 cell cycle arrest in oligodendrocyte progenitors. Development JT-Development (Cambridge, England), 1999,126(5):1077-1090.
[48]Tanaka T, Cosma MP, Wirth K, et al. Identification of cohesin association sites at centromeres and along chromosome arms. Cell JT-Cell,1999,98(6):847-858.
[49]Cosma MP, Tanaka T, Nasmyth K. Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle-and developmentally regulated promoter. Cell JT-Cell,1999,97(3):299-311.
[50]Gussoni E, Soneoka Y, Strickland CD, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature JT-Nature, 1999,401(6751):390-394.
[51]Xie T, Spradling AC. decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary. Cell JT-Cell,1998,94(2): 251-260.
[52]Quesenberry PJ, Becker P, Stewart FM. Phenotype of the engrafting stem cell in mice. Stem Cells JT-Stem cells (Dayton, Ohio),1998,16 Suppl 1:33-35.
[53]Quesenberry PJ, Becker PS. Stem cell homing:rolling, crawling, and nesting. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America,1998,95(26):15155-15157.
[54]Habibian HK, Peters SO, Hsieh CC, et al. The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit. J Exp Med JT-The Journal of experimental medicine,1998,188(2):393-398.
[55]Larochelle A, Vormoor J, Hanenberg H, et al. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy. Nat Med JT-Nature medicine,1996,2(12):1329-1337.
[56]Carballido JM, Namikawa R, Carballido-Perrig N, et al. Generation of primary antigen-specific human T-and B-cell responses in immunocompetent SCID-hu mice. Nat Med JT-Nature medicine,2000,6(1):103-106.
[57]Zanjani ED, Flake AW, Rice H, et al. Long-term repopulating ability of xenogeneic transplanted human fetal liver hematopoietic stem cells in sheep. J Clin Invest JT-The Journal of clinical investigation,1994,93(3):1051-1055.
[58]Bethel CA, Steinkirchner T, Zanjani ED, et al. Stromal microenvironment of human fetal hematopoiesis:in vitro morphologic studies. Pathobiology JT-Pathobiology:journal of immunopathology, molecular and cellular biology, 1994,62(2):99-103.
[59]Zanjani ED, Silva MR, Flake AW. Retention and multilineage expression of human hematopoietic stem cells in human-sheep chimeras. Blood Cells JT-Blood cells,1994,20(2-3):331-8; discussion 338-340.
[60]Almeida-Porada G, Porada C, Zanjani ED. Plasticity of human stem cells in the fetal sheep model of human stem cell transplantation. Int J Hematol JT-International journal of hematology,2004,79(1):1-6.
[61]Zanjani ED, Flake AW, Almeida-Porada G, et al. Homing of human cells in the fetal sheep model:modulation by antibodies activating or inhibiting very late activation antigen-4-dependent function. Blood JT-Blood,1999,94(7):2515-2522.
[62]Traycoff CM, Hoffman R, Zanjani ED, et al. Measurement of marrow repopulating potential of human hematopoietic progenitor and stem cells using a fetal sheep model. Prog Clin Biol Res JT-Progress in clinical and biological research, 1994,389:281-291.
[63]Datta S. Activation of neuroblast proliferation in explant culture of the Drosophila larval CNS. Brain Res JT-Brain research,1999,818(1):77-83.
[64]Donnelly DS, Krause DS. Hematopoietic stem cells can be CD34+ or CD34-Leuk Lymphoma JT-Leukemia & lymphoma,2001,40(3-4):221-234.
[65]Chiu RC, Zibaitis A, Kao RL. Cellular cardiomyoplasty:myocardial regeneration with satellite cell implantation. Ann Thorac Surg JT-The Annals of thoracic surgery, 1995,60(1):12-18.
[66]Friedenstein AJ, Chailakhyan RK, Gerasimov UV. Bone marrow osteogenic stem cells:in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet JT-Cell and tissue kinetics,1987,20(3):263-272.
[67]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science JT-Science,1999,284(5411):143-147.
[68]Healy L, May G, Gale K, et al. The stem cell antigen CD34 functions as a regulator of hemopoietic cell adhesion. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America, 1995,92(26):12240-12244.
[69]Titley I, Healy LE, Scott M, et al. Extent of variability inherent in measurements of CD34-positive cells in different human haemopoietic tissues. Bone Marrow Transplant JT-Bone marrow transplantation,1995,16(4):611-616.
[70]Pereira RF, Halford KW, O'Hara MD, et al. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America,1995,92(11):4857-4861.
[71]Lee JH, Kosinski PA, Kemp DM. Contribution of human bone marrow stem cells to individual skeletal myotubes followed by myogenic gene activation. Exp Cell Res JT-Experimental cell research,2005,307(1):174-182.
[72]Alexanian AR. Neural stem cells induce bone-marrow-derived mesenchymal stem cells to generate neural stem-like cells via juxtacrine and paracrine interactions. Exp Cell Res JT-Experimental cell research,2005,310(2):383-391.
[73]Kashofer K, Bonnet D. Gene therapy progress and prospects:stem cell plasticity. Gene Ther JT-Gene therapy,2005,12(16):1229-1234.
[74]Phinney DG, Isakova I. Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des JT-Current pharmaceutical design, 2005,11(10):1255-1265.
[75]Wislet-Gendebien S, Hans G, Leprince P, et al. Plasticity of cultured mesenchymal stem cells:switch from nestin-positive to excitable neuron-like phenotype. Stem Cells JT-Stem cells (Dayton, Ohio),2005,23(3):392-402.
[76]Phinney DG, Kopen G, Isaacson RL, et al. Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice:variations in yield, growth, and differentiation. J Cell Biochem JT-Journal of cellular biochemistry, 1999,72(4):570-585.
[77]Aubin JE. Bone stem cells. J Cell Biochem Suppl JT-Journal of cellular biochemistry. Supplement,1998,30-31:73-82.
[78]Thomas T, Gori F, Spelsberg TC, et al. Response of bipotential human marrow stromal cells to insulin-like growth factors:effect on binding protein production, proliferation, and commitment to osteoblasts and adipocytes. Endocrinology JT-Endocrinology,1999,140(11):5036-5044.
[79]Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology JT-Endocrinology,1999,140(4):1630-1638.
[80]Schoeberlein A, Holzgreve W, Dudler L, et al. Tissue-specific engraftment after in utero transplantation of allogeneic mesenchymal stem cells into sheep fetuses. Am J Obstet Gynecol JT-American journal of obstetrics and gynecology, 2005,192(4):1044-1052.
[81]Airey JA, Almeida-Porada G, Colletti EJ, et al. Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart. Circulation JT-Circulation, 2004,109(11):1401-1407.
[82]Digirolamo CM, Stokes D, Colter D, et al. Propagation and senescence of human marrow stromal cells in culture:a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol JT-British journal of haematology,1999,107(2):275-281.
[83]Young HE, Steele TA, Bray RA, et al. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec JT-The Anatomical record, 2001,264(1):51-62.
[84]Deans RJ, Moseley AB. Mesenchymal stem cells:biology and potential clinical uses. Exp Hematol JT-Experimental hematology,2000,28(8):875-884.
[85]Guerriero A, Worford L, Holland HK, et al. Thrombopoietin is synthesized by bone marrow stromal cells. Blood JT-Blood,1997,90(9):3444-3455.
[86]Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science JT-Science,1997,276(5309):71-74.
[87]Wilson SE, He YG, Weng J, et al. Effect of epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, on proliferation, motility and differentiation of human corneal epithelial cells. Exp Eye Res JT-Experimental eye research,1994,59(6):665-678.
[88]Crosbie OM, Reynolds M, McEntee G, et al. In vitro evidence for the presence of hematopoietic stem cells in the adult human liver. Hepatology JT-Hepatology (Baltimore, Md.),1999,29(4):1193-1198.
[89]Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science JT-Science,1999,284(5417):1168-1170.
[90]Liu J, Xue L. [The regulatory mechanism of liver oval cell differentiation.]. Zhonghua Gan Zang Bing Za Zhi,2005,13(12):951-953.
[91]Ichiba M, Shimomura T, Murai R, et al. Dual effects of adenovirus-mediated thrombopoietin gene transfer on hepatic oval cell proliferation and platelet counts. Biochem Biophys Res Commun JT-Biochemical and biophysical research communications,2005,335(3):723-729.
[92]Jeong WI, Jeong DH, Do SH, et al. Expression of cytokeratins 8 and 18 on Mallory body and oval cell in rats during hepatic fibrosis. In Vivo JT-In vivo (Athens, Greece),2005,19(4):769-775.
[93]Lazaro CA, Rhim JA, Yamada Y, et al. Generation of hepatocytes from oval cell precursors in culture. Cancer Res JT-Cancer research,1998,58(23):5514-5522.
[94]Pi L, Oh SH, Shupe T, et al. Role of connective tissue growth factor in oval cell response during liver regeneration after 2-AAF/PHx in rats. Gastroenterology JT-Gastroenterology,2005,128(7):2077-2088.
[95]Subrata LS, Lowes KN, Olynyk JK, et al. Hepatic expression of the tumor necrosis factor family member lymphotoxin-beta is regulated by interleukin (IL)-6 and IL-lbeta:transcriptional control mechanisms in oval cells and hepatoma cell lines. Liver Int JT-Liver international:official journal of the International Association for the Study of the Liver,2005,25(3):633-646.
[96]Kofman AV, Morgan G, Kirschenbaum A, et al. Dose-and time-dependent oval cell reaction in acetaminophen-induced murine liver injury. Hepatology JT Hepatology (Baltimore, Md.),2005,41(6):1252-1261.
[97]Brooling JT, Campbell JS, Mitchell C, et al. Differential regulation of rodent hepatocyte and oval cell proliferation by interferon gamma. Hepatology JT Hepatology (Baltimore, Md.),2005,41(4):906-915.
[98]Zajicek G, Oren R, Weinreb M Jr. The streaming liver. Liver JT-Liver, 1985,5(6):293-300.
[99]Forbes SJ, Themis M, Alison MR, et al. Synergistic growth factors enhance rat liver proliferation and enable retroviral gene transfer via a peripheral vein. Gastroenterology JT-Gastroenterology,2000,118(3):591-598.
[100]Werlich T, Stiller KJ, Machnik G. Experimental studies on the stem cell concept of liver regeneration. Ⅱ. Exp Toxicol Pathol JT-Experimental and toxicologic pathology:official journal of the Gesellschaft fur Toxikologische Pathologie,1999,51(1):93-98.
[101]Preisegger KH, Factor VM, Fuchsbichler A, et al. Atypical ductular proliferation and its inhibition by transforming growth factor betal in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model for chronic alcoholic liver disease. Lab Invest JT-Laboratory investigation; a journal of technical methods and pathology,1999,79(2):103-109.
[102]Lemire JM, Shiojiri N, Fausto N. Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine. Am J Pathol JT-The American journal of pathology,1991,139(3):535-552.
[103]Shiojiri N, Lemire JM, Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Res JT-Cancer research,1991,51(10):2611-2620.
[104]Cubero FJ, Maganto P, Mula N, et al. Hepatic proliferation in Gunn rats transplanted with hepatocytes:effect of retrorsine and tri-iodothyronine. Cell Prolif JT-Cell proliferation,2009,38(3):137-146.
[105]Dahlke MH, Popp FC, Bahlmann FH, et al. Liver regeneration in a retrorsine/CCl4-induced acute liver failure model:do bone marrow-derived cells contribute?. J Hepatol JT-Journal of hepatology,2009,39(3):365-373.
[106]Cereghini S. Liver-enriched transcription factors and hepatocyte differentiation. FASEB J JT-The FASEB journal:official publication of the Federation of American Societies for Experimental Biology,1996,10(2):267-282.
[107]Lazennec G, Kern L, Valotaire Y, et al. The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout estrogen receptor gene through enhancing autoregulation. Mol Cell Biol JT-Molecular and cellular biology, 1997,17(9):5053-5066.
[108]Tanaka T, Yoshida N, Kishimoto T, et al. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO J JT-The EMBO journal,1997,16(24):7432-43.
[109]Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature JT-Nature,2009,406(6793):257.
[110]Kim TH, Mars WM, Stolz DB, et al. Extracellular matrix remodeling at the early stages of liver regeneration in the rat. Hepatology JT-Hepatology (Baltimore, Md.),2009,26(4):896-904.
[111]Yin L, Ghebranious N, Chakraborty S, et al. Control of mouse hepatocyte proliferation and ploidy by p53 and p53ser246 mutation in vivo. Hepatology JT-Hepatology (Baltimore, Md.),2008,27(1):73-80.
[112]Najimi M, Sokal E. Liver cell transplantation. Minerva Pediatr JT Minerva pediatrica,2009,57(5):243-257.
[1]Pertersen BE. Hepatic"stem"cells:coming full circle[J]. B loodcellsMol D is, 2001,27 (3):590.
[2]BeschornerWE, Civin CI, StraussLC. Localization of hematopoi2etic p rogenitor cells in tissue with the anti2My210 monoclonal anti2body[J]. Am J Pathol,1985, 119(1):1-4.
[3]Radaeva (Pronina) SA, Faktor VM. The differentiation of ovalcells into hepartocytes during induced hepatic carcinogenesis inmice. An electron microscop ic study [J]. Tsitologiia,1990,32 (4):331-336.
[4]FaktorVM, Radaeva SA. The formation of oval2cell ducts duringhepatic carcinogenesis in mice. Its relationship to the p re2exitingcanals of Hering[J]. Ontogenez,1992,23 (4):407-418.
[5]Kennedy S, Rettinger S, Flye MW, et al. Experiments in trans2genic mice show that hepatocytes are the source for postnatal livergrowth and do not stream[J]. Hepatology,1995,22:160-168.
[6]Burke ZD, Shen CN, Ralphs KL, et al. Characterization of liverfunction in transdifferentiated hepatocytes [J]. J Cell Physiol,2006,206 (1):147-159.
[7]Petersen BE, BowenWC, Patrene KD, et al. Bone marrow as apotential source of hepatic oval cells[J]. Science,1999,284:1168-1170.
[8]GrompeM. The role of bone marrow stem cells in liver regenera2tion[J]. Sem in L iverD is,2003,23 (4):363-372.
[9]Oh SH, Witek RP, Bae SH, et al. Bone marrow2derived hepaticoval cells differentiate into hepatocytes in 22acetylaminofluorene/partial hepatectomy2induced liver regeneration[J]. Gastroenterology,2007,132 (3):1077-1087.
[10]Wang X, FosterMA, A12Dhalimym, et al. The origin and liver re2population capacity of murine oval cells [J]. Proc N atl Acad Sci USA,2003,100:11881 11888.
[11]Szabo E, Lodi C, Korpos E, et al. Exp ression ofmatrilin22 in ovalcells during rat liver regeneration[J]. Matrix B iol,2007,21.
[12]YovchevMI, Grozdanov PN, Joseph B, et al. Novel hepatic p ro2genitor cell surface markers in the adult rat liver[J]. Hepatology,2007,45 (1):139-149.
[13]Grozdanov PN, YovchevMI, Dabeva MD. The oncofetal p roteinglyp ican23 is a novelmarker of hepatic p rogenitor/oval cells[J]. Lab Invest,2006,86 (12):1272-1284.
[14]SoltDB, Cayama E, Tsuda H, et al. Promotion of liver cancer de2velopment by brief exposure to dietary 22acetylaminofluorene p luspartial hepatectomy or carbon tetrachloride [J]. Cacer Res,1983,43 (1):188-191.
[15]Ise N, Sato T, Yasui O, et al. Enhanced p roliferation of hepaticp rogenitor cells in rats after portal branch occlusion [J]. Liver Transpl,2004,10 (6):748-754.
[16]SuzukiA, Zheng YW, Kondo R, et al. Flow2cytometric separationand enrichment of hepatic p rogenitor cells in the develop ingmouseliver[J]. J Hepatology,2000,32 (6):1230-1239.
[17]Gordon GJ, Butz GM, Grisham JW, et al. Isolation short2termculture and transp lantation of small hepatocyte21ike p rogenitor cellsfrom retrorisine2exposed rats[J]. J Transplantation,2002,73 (8):1236-1243.
[18]王宇明,陈耀凯,郎松等。大鼠肝卵圆细胞的分离培养及脾内移植研究[J].中华肝脏病杂志,2003,6(11)：328-330.
[19]Nakauchi H. Isolation and clonal characterization of hematopoieticand liver stem cells[J]. Cornea,2004,23 (8 Supp 1):S2-7.
[20]Stamp L, Crosby HA, Hawes SM, et al. A novel cell2surfacemarker found on human embryonic hepatoblasts and a subpopulation of hepatic biliary ep ithelial cells [J]. S tem Cells,2005,23 (1):103-112.
[21]Monga SP, Tang Y, Candotti F, et al. Exapansion of hepatic andhematopoietic stem cells utilizing mouse embryonic liver exp lants [J]. Cell Transplant,2001,10 (1):81-89.
[22]Zheng D, Oh SH, Jung Y, Petersen BE. Oval cell response in 22acetylamino-fluorene/partial hepatectomy rat is attenuated by shortinterfering RNA targeted to stromal cell2derived factor21 [J]. Am JPathol,2006,169 (6):2066-2074.
[23]Piscaglia AC, Shupe TD, Oh SH, et al. Granulocyte2colony stimulating factor p romotes liver repair and induces oval cell migrationand p roliferation in rats[J]. Gastroenterology,2007,133 (2):619-631.
[24]Suzuki A, Zheng YW, Fukao K, et al. Hepatic stem/p rogenitorcellswith high p roliferative potential in liver organ formation [J]. Transplantation Proceeding,2001, 33:585-586.
[25]He ZP, TanWQ, Tanq YF, et al. Activation isolation identifica2tion and in vitro p roliferation of oval cells from adult rat livers[J]. Cell Prolif,2004,37 (2):177-187.
[26]Chen JZ, Hong H, Xiang J, et al. A selective trop ism of transfused oval cells for liver[J]. World J Gastroenterol,2003,9:544-546.
[27]Machi H, Irani AN, Gagandeep S, et al. Isolation of human p rogenitor liver ep ithelial cellswith extensive rep lication capacity and differentiation into mature hepatocytes[J]. J Cell Sci,2002,115 (10):2679.
[28]薛玲,廖冰,赵国强,等,大鼠肝癌形成过程中癌基因表达变化的意义[J].世界华人消化杂志,2003,11：904-907.
[29]DumbleML, Croager EJ, Yeoh GC. Generation and characterization of p53 null transformed hepatic p rogenitor cells, oval cellsgive rise tohepatocellular carcinoma [J]. Carcinogenesis,2002,23:435-445.
[30]TsamandasAC, Syrokosta I, Thomopoulos K, et al. Potential role of hepatic p rogenitor cells exp ression in cases of chronic hepatitis Cand their relation to response to theropy:a clinicopathop logic study [J]. L iver Int,2006,26 (7):817-826.
[31]Katoonizadeh A, Nevens F, Verslype C, et al. Liver regeneration in acute severe liver impairment:a clinicopathological correlation study[J]. L iver Int,2006,26 (10): 1225-1233.
[32]KusanoM, MitoM. Observations on the fine structure of ling survived hepatocytes inoculated into rat sp leen[J]. Gastroenterology,1982,82:616-628.
[33]Avital I, Feraresso C, Aoki T, et al. Bone marrow2derival liver stem cell and mature hepatocyte engraftment in livers undergoing rejection[J]. Surgery,2000,132: 384-390.
[34]Matsusaka S, Toyosaka A, Nakasho K, et al. The role of oval cells in rat hepaticyte transp lantation[J]. Transplation,2000,70:441-446.
[35]Fang B, ShiM, Liao L, et al. Systemic infusion of FLKI (+) mesenchymal stem cells ameliorate carbon tetrachloride2induced liver fibrosis in mice[J]. Transplation, 2004,78 (1):83-88.
[36]Yu Y, Yao AH, Chen N, et al. Mesenchymal stem cells over exp ressing hepatocyte growth factor imp rove small2for2size liver graftsregeneration[J]. M ol Ther,2007:22.
[37]姚鹏,胡大荣,王帅等。人自体骨髓干细胞移植治疗慢性肝功能衰竭的研究[J].中华肝脏病杂志,2005,13：941-942。
[38]Gupa DK, Sharma S, Venugopal P, et al. Transp lant Proc,2007Ap r; 39 (3): 700-702.
[2]李才主编,器官纤维化基础与临床。北京：人民卫生出版社,2003,44-70。
[3]程明亮,杨长青主编,肝纤维化基础研究及临床。(第二版)北京：人民卫生出版社,2002,20-30。
[4]漆德芳主编, 肝硬化。 北京：北京科学技术出版社,2000,85-90。
[5]厉有名,中国酒精性肝病的研究现状。现代消化及介入诊疗,2007,12(4)：235-236.
[6]Refik Mas M, Comert B, Oncu K, et al. The effect of taurine treatment on oxidative stress in experimental liver fibrosis. Hepatol Res,2008,28(4):207-215.
[7]de Bleser PJ, Jannes P, van Buul-Offers SC, et al. Insulinlike growth factor-II/mannose 6-phosphate receptor is expressed on CC14-exposed rat fat-storing cells and facilitates activation of latent transforming growth factor-beta in cocultures with sinusoidal endothelial cells. Hepatology JT,1995,21(5):1429-1437.
[8]王宝恩,王泰龄,等.复方861对肝星状细胞增殖和凋亡的干预作用.中华肝脏病杂志,2000,8：78-80.
[9]Yao XX, Tang YW, Yao DM, et al. Effects of Yigan Decoction on proliferation and apoptosis of hepatic stellate cells. World J Gastroenterol,2002,8(3):511-514.
[10]Novobrantseva TI, Majeau GR, Amatucci A, et al. Attenuated liver fibrosis in the absence of B cells. J Clin Invest,2005,115(11):3072-3082.
[11]Bataller R, Brenner DA. Liver fibrosis. J Clin Invest JT-The Journal of clinical investigation,2005,115(2):209-218.
[12]Wright MC, Issa R, Smart DE, et al. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology,2001,121(3):685-698.
[13]梁扩寰.肝脏病学[M].北京：人民卫生出版社,1995.234-235.
[14]华海婴,郭旭光,杨波,肝纤维化的治疗和展望。医药导报,2007,26(4) 405-407。
[15]晁岚,张慧琴等,人胚胎干细胞的研究进展。现代妇产科进展,2003,12(4)：293-297
[16]Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature JT-Nature,2008,418(6893):41-49.
[17]Ortiz LA, Gambelli F, McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A,2003,100(14):8407-8411.
[18]Sakaida I, Terai S, Yamamoto N, et al. Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice. Hepatology,2008,40(6):1304-1311.
[19]Mangi AA, Noiseux N, Kong D, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med, 2003,9(9):1195-1201.
[20]Zhao DC, Lei JX, Chen R, et al. Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol, 2005,11(22):3431-3440.
[21]Carvalho AB, Quintanilha LF, Dias JV, Paredes BD, Mannheimer EG. Bone marrow multipotent mesenchymal stromal cells do not reduce fibrosis or improve function in a rat model of severe chronic liver injury. Stem Cells.2008,26(5): 1307-1314
[22]Quintanilha LF, Mannheimer EG, Carvalho AB, Paredes BD, Dias JV. Bone marrow cell transplant does not prevent or reverse murine liver cirrhosis. Cell Transplant.2008;17(8):943-953
[23]Malhi H, Gupta S. Hepatocyte transplantation:new horizons and challenges. J Hepatobiliary Pancreat Surg 2001,8(1):40-50.
[24]Shiojiri N, Lemire JM, Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Res 1991;51:2611-2620.
[25]Shiojiri N. The origin of intrahepatic bile duct cells in the mouse. J Embryol Exp Morphol 1984;79:25-39.
[26]Alison MR. Liver stem cells:implications for hepatocarcinogenesis. Stem Cell Rev.2005;1(3):253-260
[27]Ln Guo-yue, Zhang Ping, Li Hong, Li Shuang, Wang Guang-yi et al. Isolation, culture and identification of adult hepatic stem cells in vitro. Journal of Clinical Rehabilitative Tissue Engineering Research 2007;50:10169-10172
[28]Abelev Gl. Eraiser TL. Cellular aspeccts of alpha-fetoprotein re-expression in tumors. Semin Cancer Biol 1999:9(2):95 - 107
[29]Ishikawa K. Sasaki A, Haraguchi N,et al. A case of an alpha-fetoprotein-producing intrahepatic cholangiocarcinoma suggests probable cancer stem cell origin. Omcologist 2007:12(3):320-324
[30]Sell S, Osborn K, Leffert HL. Autoradiography of "oval cells" appearing rapidly in the livers of rats fed N-2-fluorenylacetamide in a choline devoid diet. Carcinogenesis 1981;2:7-14.
[31]Sell S, Salman J. Light-and electron-microscopic autoradiographic analysis of proliferating cells during the early stages of chemical hepatocarcinogenesis in the rat induced by feeding N-2-fluorenylacetamide in a choline-deficient diet. Am J Pathol 1984; 114:287-300.
[32]Evarts RP, Nagy P, Nakatsukasa H, Marsden E, Thorgeirsson SS. In vivo differentiation of rat liver oval cells into hepatocytes. Cancer Res 1989;49:1541-1547.
[33]Novikoff PM, Yam A, Oikawa I.Blast-like cell compartment in carcinogen-induced proliferating bile ductules. Am J Pathol 1996; 148:1473-1492.
[34]Bisgaard HC, Nagy P, Santoni-Rugiu E, Thorgeirsson SS.Proliferation, apoptosis, and induction of hepatic transcription factors are characteristics of the early response of biliary epithelial (oval) cells to chemical carcinogens. Hepatology 1996;23:62-70.
[35]Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature,2000,406(6793):257.
[36]Theise ND, Nimmakayalu M, Gardner R, et al. Liver from bone marrow in humans. Hepatology,2000,32(1):11-16.
[37]Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science 1999;284:1168-1170.
[38]Bryon E. Petersen, Brian Grossbard, et al. Mouse A6-Positive Hepatic Oval Cells Also Express Several Hematopoietic Stem Cell Markers. Hepatology,2003,37(3): 632-640.
[39]Gordon GJ. Butz GM, Grisham JW, et al.Isolation, short-term culture, and transplantatiOn of small hepatocyte-like progenitor cells from retrosisine. exposed rats. Tmnsplantation 2002; 73(8):1236-1243
[40]Suzuki A、Zheng Y w. Kondo R et al. Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver。Hepatology。 2000; 32(6):1230-1239
[41]Lv Guo-yue, Zhang Ping, Li Hong, Li Shuang, Wang Guang-yi et al. Isolation, culture and identification of adult hepatic stem cells in vitro. Journal of Clinical Rehabilitative Tissue Engineering Research 2007;50:10169-10172
[42]居胜红,滕皋军,陆海华等,大鼠间充质干细胞超顺磁性氧化铁标记和经脾移植后的MR示踪研究。中华放射学杂志,2006,40(2)：127-132.
[43]Suzuki A、Zheng Y w. Kondo R et al. Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver。 Hepatology。 2000; 32(6):1230.1239
[44]Seglen PO. Prenparation of isolated rat live cells. Methods Cell Biol1976; 13: 29-83
[45]Avital I, lnderbizin D. Aoki et al isolation, characte rization, and transDlantation of bone marrow-derived hepatocyte stem cells Biochem Biophys Res Commun 2001; 288(11):156-166
[46]Gordon GJ. Butz GM, Grisham JW, et al.Isolation, short-term culture, and transplantatiOn of small hepatocyte-like progenitor cells from retrosisine. exposed rats. Tmnsplantation 2002; 73(8):1236-1243
[47]Taniguchi H. Suzuki A, Zheng et al. Usefulness of flow cytometric cell sorting for enrichment of hepatic stem and progenitor cells in the liver. Transpiant Proc 2000; 32(21:249-251
[48]Lv Guo-yue, Zhang Ping, Li Hong, Li Shuang, Wang Guang-yi et al. Isolation, culture and identification of adult hepatic stem cells in vitro. Journal of Clinical Rehabilitative Tissue Engineering Research 2007;50:10169-10172
[49]Faris RA,Konkin T,Halpert G.Liver stem cells:apotential source of hepatocytes for the treatment of human liver disease.Artifi Organs,2001,25(7):513-521
[50]Matsusaka S,Toyosaka A,Nakasho K,et al.The role of oval cells in rats hepatocyte transplantation. Transplantation,2000,70(3):441-446
[51]Yasui O, Miura N, Terada K, et al.Isolation of oval cells from long-evans cinnamon rats and their transplantation into hepatocytes in vivo in the rat liver.Hepatology,1997,25(2):329-334
[52]杜智,李涛,张金卷,朱争艳等,肝干细胞移植治疗大鼠爆发性肝功能衰竭的实验研究。生物医学工程与临床,2006 10(6)：346-349
[53]Monga SP, Tang Y, Candotti F,et al.Expansion of hepatic and hematopoietic stemcells utilizing mouse embryonic liver explants. Cell Transplant,2001,10 (1):81-89.
[54]Strom S C, Fisher R A, Thompson M T, et al. Hepatocyte transplantation as a bridge to ortho-topic liver transplantation in terminal liver faliure. Transplantation, 1997,63:559-567
[55]Emerson RW. Human hepatocyte transplantation:gene therapy and more? Pediatrics,1998,102:647-659
[56]ArkadopoulosN, LiljaH, SuhKS, etal. Introsplenic transplantation of allogenic hepatocytes pro-longs survival in anhepatic trts. Hepatology,1998,28:1365-1376
[57]Chatterjee S, Vrolix G, Depoortere I, Peeters T, Van Marck E. The therapeutic effect of the neuropeptide hormone somatostatin on Schistosoma mansoni caused liver fibrosis. BMC Infect Dis 2005; 5:45
[58]Sato R, Maesawa C, Fujisawa K, Wada K, Oikawa K, Takikawa Y, Suzuki K, Oikawa H, Ishikawa K, Masuda T. Prevention of critical telomere shorten-ing by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis. Gut 2004; 53:1001-1009
[59]Liu QH, Li DG, Huang X, Zong CH, Xu QF, Lu HM. Suppressive effects of 17beta-estradiol on hepatic fibrosis in CC14-induced rat model. World J Gastroenterol 2004; 10:1315-1320
[60]Shi MX, Fang BJ, Liao LM, Yang SG, Liu YH, Zhao CH. Flkl+ mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Shengwu Gongcheng Xuebao 2005; 21:396-401
[61]Kang JS, Wanibuchi H, Morimura K, Puatanachok-chai R, Salim El, Hagihara A, Seki S, Fukushima S. Enhancement by estradiol 3-benzoate in thioaceta-mide-induced liver cirrhosis of rats. Toxicol Sci 2005; 85:720-726
[62]Hata J, Ikeda E, Uno H, Asano S. Expression of hepatocyte growth factor mRNA in rat liver cirrhosis induced by N-nitrosodimethylamine as evidenced by in situ RT-PCR. J Histochem Cytochem 2002; 50:1461-1468
[63]Sakaida I, Hironaka K, Terai S, Okita K. Gadolinium chloride reverses dimethylnitrosamine (DMN)-induced rat liver fibrosis with increased matrix metalloproteinases (MMPs) of Kupffer cells. Life Sci 2003; 72:943-959
[64]Brond L, Hadrup N, Salling N, Torp M, Graebe M, Christensen S, Nielsen S, Jonassen TE. Uncoupling of vasopressin signaling in collecting ducts from rats with CBL-induced liver cirrhosis. Am J Physiol Renal Physiol 2004; 287:F806-F815
[65]Li J, Niu JZ, Wang JF, Li Y, Tao XH. Pathological mechanisms of alcohol-induced hepatic portal hypertension in early stage fibrosis rat model. World J Gastroenterol 2005; 11:6483-6488
[66]Zhao DC, Lei JX, Chen R, et al. Bone marrow-derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroenterol, 2005,11(22):3431-3440.
[67]Gao J, Dennis JE, Muzic RF, et al. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs,2001, 169(1):12-20.
[68]Naughton MA, Walport MJ, Wurzner R, et al. Organ-specific contribution to circulating C7 levels by the bone marrow and liver in humans. Eur J Immunol, 1996,26(9):2108-2112.
[69]Alison MR, Poulsom R, Forbes SJ. Update on hepatic stem cells. Liver, 2001,21(6):367-373.
[70]Avital I, Inderbitzin D, Aoki T, et al. Isolation, characterization, and transplant- tation of bone marrow-derived hepatocyte stem cells. Biochem Biophys Res Commun, 2001,288(1):156-164.
[71]Brill S, Holst P, Sigal S, et al. Hepatic progenitor populations in embryonic, neonatal, and adult liver. Proc Soc Exp Biol Med,1993,204(3):261-269.
[72]Braun KM, Sandgren EP. Cellular origin of regenerating parenchyma in a mouse model of severe hepatic injury.Am J Pathol,2000,157(2):561-569.
[73]Petersen BE. Hepatic "stem"cells:coming full circle. Blood cells Mol Dis,2001,27(3):590-600.
[74]Ohashi K,Park F,Kay MA.Hepatocyte transplantation:clinical and experimental application J Mol Med,2001,79(11):617-630.
[1]Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science JT-Science,1998,282(5391):1145-1147.
[2]Boiani M, Eckardt S, Scholer HR, et al. Oct4 distribution and level in mouse clones:consequences for pluripotency. Genes Dev JT-Genes & development, 2002,16(10):1209-1219.
[3]Suemori H, Tada T, Torii R, et al. Establishment of embryonic stem cell lines from cynomolgus monkey blastocysts produced by IVF or ICSI. Dev Dyn JT Developmental dynamics:an official publication of the American Association of Anatomists,2001,222(2):273-279.
[4]Jackson KA, Mi T, Goodell MA. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America,1999,96(25): 14482-14486.
[5]Almeida-Porada G, Porada C, Zanjani ED. Adult stem cell plasticity and methods of detection. Rev Clin Exp Hematol JT-Reviews in clinical and experimental hematology,2001,5(1):26-41.
[6]Forbes SJ, Vig P, Poulsom R, et al. Adult stem cell plasticity:new pathways of tissue regeneration become visible. Clin Sci (Lond) JT-Clinical science (London, England:1979),2002,103(4):355-369.
[7]Slack JM. Stem cells in epithelial tissues. Science JT-Science,2000,287(5457): 1431-3.
[8]Tropepe V, Coles BL, Chiasson BJ, et al. Retinal stem cells in the adult mammalian eye. Science JT-Science,2000,287(5460):2032-2036.
[9]van der Kooy D, Weiss S. Why stem cells?. Science JT-Science,2000,287(5457): 1439-1441.
[10]Loeffler M, Roeder I. Tissue stem cells:definition, plasticity, heterogeneity, self-organization and models-a conceptual approach. Cells Tissues Organs JT-Cells, tissues, organs,2002,171(1):8-26.
[11]Coulombel L. [Adult tissue stem cells:definition, identification and therapeutic use]. Journ Annu Diabetol Hotel Dieu JT-Journees annuelles de diabetologie de 1'Hotel-Dieu,2003:1-16.
[12]Parker GC, Anastassova-Kristeva M, Eisenberg LM, et.al. Stem cells:shibboleths of development, part Ⅱ:Toward a functional definition. Stem Cells Dev JT-Stem cells and development,2005,14(5):463-469.
[13]Burgin MT, Burkli P. [Embryos and embryo-like entities:problem of definition in the draft of the Swiss embryonic research law]. Ther Umsch JT-Therapeutische Umschau. Revue therapeutique,2002,59(11):613-617.
[14]Okano H. [Identification of neural stem cells in adult human brain:its implication in the strategy for repairing the damaged central nervous system]. Rinsho Shinkeigaku JT-Rinsh inverted question mark shinkeigaku= Clinical neurology,2005,45(11): 871-873.
[15]Bianchi de Di Risio CC, Callero F, Hidalgo A, et al.[Mesenchymal stem cells.Differentiation and alternative source of neural tissue]. Medicina (B Aires) JT-Medicina,2004,64(6):543-549.
[16]Chertkov IL, Drize NI. ["Plasticity" of bone marrow stem cells]. Ter Arkh JT-Terapevticheskii arkhiv,2004,76(7):5-11.
[17]Weissman IL. Medicine:politic stem cells. Nature JT-Nature,2006,439 (7073):145-7.
[18]Weissman IL. Stem cells:units of development, units of regeneration, and units in evolution. Cell JT-Cell,2000,100(1):157-168.
[19]Stevens D. Embryonic stem cell research:will President Bush's limitation on federal funding put the United States at a disadvantage? A comparison between U.S. and international law. Houst J Int Law JT-Houston journal of international law, 2003,25(3):623-653.
[20]Cotsarelis G, Kaur P, Dhouailly D, et al. Epithelial stem cells in the skin: definition, markers, localization and functions. Exp Dermatol JT-Experimental dermatology,1999,8(1):80-68.
[21]Li A, Simmons PJ, Kaur P. Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America, 1998,95(7):3902-3907.
[22]Tuoya, Hirayama K, Nagaoka T, et al. Identification of cell surface marker candidates on SV-T2 cells using DNA microarray on DLC-coated glass. Biochem Biophys Res Commun JT-Biochemical and biophysical research communications, 2005,334(1):263-268.
[23]David R, Groebner M, Franz WM. Magnetic cell sorting purification of differentiated embryonic stem cells stably expressing truncated human CD4 as surface marker. Stem Cells JT-Stem cells (Dayton, Ohio),2005,23(4):477-482.
[24]Stamp L, Crosby HA, Hawes SM, et al. A novel cell-surface marker found on human embryonic hepatoblasts and a subpopulation of hepatic biliary epithelial cells. Stem Cells JT-Stem cells (Dayton, Ohio),2005,23(1):103-112.
[25]Ko IK, Kato K, Iwata H. Antibody microarray for correlating cell phenotype with surface marker. Biomaterials JT-Biomaterials,2005,26(6):687-696.
[26]Fukada S, Higuchi S, Segawa M, et al. Purification and cell-surface marker characterization of quiescent satellite cells from murine skeletal muscle by a novel monoclonal antibody. Exp Cell Res JT-Experimental cell research,2004,296(2): 245-255.
[27]Kang EM, Zickler PP, Burns S, et al. Hematopoietic stem cell transplantation prevents diabetes in NOD mice but does not contribute to significant islet cell regeneration once disease is established. Exp Hematol JT-Experimental hematology, 2005,33(6):699-705.
[28]Singh Roy N, Nakano T, Xuing L, et al. Enhancer-specified GFP-based FACS purification of human spinal motor neurons from embryonic stem cells. Exp Neurol JT-Experimental neurology,2005,196(2):224-234.
[29]Fujimura J, Ogawa R, Mizuno H, et al. Neural differentiation of adipose-derived stem cells isolated from GFP transgenic mice. Biochem Biophys Res Commun JT-Biochemical and biophysical research communications,2005,333(1):116-121.
[30]Xia Z, Ye H, Locklin RM, et al. Efficient characterisation of human cell-bioceramic interactions in vitro and in vivo by using enhanced GFP-labelled mesenchymal stem cells. Biomaterials JT-Biomaterials,2005,26(29):5790-5800.
[31]Morgan DO.Principles of CDK regulation.Nature JT-Nature,1995,374(6518): 131-134.
[32]Ohshima T, Gilmore EC, Longenecker G, et al. Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous. J Neurosci JT-The Journal of neuroscience:the official journal of the Society for Neuroscience,1999,19(14): 6017-6026.
[33]Sondhi SM, Singh N, Kumar A, et al. Synthesis, anti-inflammatory, analgesic and kinase (CDK-1, CDK-5 and GSK-3) inhibition activity evaluation of benzimidazole/ benzoxazole derivatives and some Schiff s bases. Bioorg Med Chem,2006.
[34]Uziel T, Zindy F, Sherr CJ, et al. The CDK Inhibitor pl8(Ink4c) is a Tumor Suppressor in Medulloblastoma. Cell Cycle,2006,5(4).
[35]Dai Y, Hamm TE, Dent P, et al. Cyclin D1 Overexpression Increases the Susceptibility of Human U266 Myeloma Cells to CDK Inhibitors Through a Process Involving p130-, p107-and E2F-Dependent S Phase Entry. Cell Cycle,2006,5(4).
[36]Zannoni GF, Faraglia B, Tarquini E, et al. Expression of the CDK inhibitor p27(kip1) and oxidative DNA damage in non-neoplastic and neoplastic vulvar epithelial lesions. Mod Pathol,2006.
[37]Chou HY, Chou HT, Lee SC. Cdk-dependent activation of poly(ADP-ribose) polymerase member 10 (PARP10). J Biol Chem,2006.
[38]Coleman ML, Densham RM, Croft DR, et al. Stability of p21(Wafl/Cipl) CDK inhibitor protein is responsive to RhoA-mediated regulation of the actin cytoskeleton. Oncogene,2006.
[39]Pang L, Reddy PV, McAuliffe CI, et al. Studies on BrdU labeling of hematopoietic cells:stem cells and cell lines. J Cell Physiol JT-Journal of cellular physiology,2003,197(2):251-260.
[40]Van Bockstaele DR, Lardon F, Snoeck HW, et al. BrdU-Hoechst-ethidium bromide (EB) quenching technique for studying kinetics of hematopoiesis. Blood JT- Blood,1992,80(1):289-291.
[41]Pietrzyk ME, Priestley GV, Wolf NS. Normal cycling patterns of hematopoietic stem cell subpopulations:an assay using long-term in vivo BrdU infusion. Blood JT Blood,1985,66(6):1460-1462.
[42]Oostendorp RA, Audet J, Eaves CJ. High-resolution tracking of cell division suggests similar cell cycle kinetics of hematopoietic stem cells stimulated in vitro and in vivo. Blood JT-Blood,2000,95(3):855-862.
[43]Shaaban AF, Kim HB, Milner R, et al. A kinetic model for the homing and migration of prenatally transplanted marrow. Blood JT-Blood,1999,94(9): 3251-3257.
[44]Flake AW, Zanjani ED. In utero hematopoietic stem cell transplantation: ontogenic opportunities and biologic barriers. Blood JT-Blood,1999,94(7): 2179-2191.
[45]Caldwell MC, Datta S. Expression of cyclin E or DP/E2F rescues the G1 arrest of trol mutant neuroblasts in the Drosophila larval central nervous system. Mech Dev JT-Mechanisms of development,1998,79(1-2):121-130.
[46]Ghiani CA, Yuan X, Eisen AM, et al. Voltage-activated K+ channels and membrane depolarization regulate accumulation of the cyclin-dependent kinase inhibitors p27(Kipl) and p21(CIP1) in glial progenitor cells. J Neurosci JT-The Journal of neuroscience:the official journal of the Society for Neuroscience, 1999,19(13):5380-5392.
[47]Ghiani CA, Eisen AM, Yuan X, et al. Neurotransmitter receptor activation triggers p27(Kip1)and p21(CIP1) accumulation and G1 cell cycle arrest in oligodendrocyte progenitors. Development JT-Development (Cambridge, England), 1999,126(5):1077-1090.
[48]Tanaka T, Cosma MP, Wirth K, et al. Identification of cohesin association sites at centromeres and along chromosome arms. Cell JT-Cell,1999,98(6):847-858.
[49]Cosma MP, Tanaka T, Nasmyth K. Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle-and developmentally regulated promoter. Cell JT-Cell,1999,97(3):299-311.
[50]Gussoni E, Soneoka Y, Strickland CD, et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature JT-Nature, 1999,401(6751):390-394.
[51]Xie T, Spradling AC. decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary. Cell JT-Cell,1998,94(2): 251-260.
[52]Quesenberry PJ, Becker P, Stewart FM. Phenotype of the engrafting stem cell in mice. Stem Cells JT-Stem cells (Dayton, Ohio),1998,16 Suppl 1:33-35.
[53]Quesenberry PJ, Becker PS. Stem cell homing:rolling, crawling, and nesting. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America,1998,95(26):15155-15157.
[54]Habibian HK, Peters SO, Hsieh CC, et al. The fluctuating phenotype of the lymphohematopoietic stem cell with cell cycle transit. J Exp Med JT-The Journal of experimental medicine,1998,188(2):393-398.
[55]Larochelle A, Vormoor J, Hanenberg H, et al. Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy. Nat Med JT-Nature medicine,1996,2(12):1329-1337.
[56]Carballido JM, Namikawa R, Carballido-Perrig N, et al. Generation of primary antigen-specific human T-and B-cell responses in immunocompetent SCID-hu mice. Nat Med JT-Nature medicine,2000,6(1):103-106.
[57]Zanjani ED, Flake AW, Rice H, et al. Long-term repopulating ability of xenogeneic transplanted human fetal liver hematopoietic stem cells in sheep. J Clin Invest JT-The Journal of clinical investigation,1994,93(3):1051-1055.
[58]Bethel CA, Steinkirchner T, Zanjani ED, et al. Stromal microenvironment of human fetal hematopoiesis:in vitro morphologic studies. Pathobiology JT-Pathobiology:journal of immunopathology, molecular and cellular biology, 1994,62(2):99-103.
[59]Zanjani ED, Silva MR, Flake AW. Retention and multilineage expression of human hematopoietic stem cells in human-sheep chimeras. Blood Cells JT-Blood cells,1994,20(2-3):331-8; discussion 338-340.
[60]Almeida-Porada G, Porada C, Zanjani ED. Plasticity of human stem cells in the fetal sheep model of human stem cell transplantation. Int J Hematol JT-International journal of hematology,2004,79(1):1-6.
[61]Zanjani ED, Flake AW, Almeida-Porada G, et al. Homing of human cells in the fetal sheep model:modulation by antibodies activating or inhibiting very late activation antigen-4-dependent function. Blood JT-Blood,1999,94(7):2515-2522.
[62]Traycoff CM, Hoffman R, Zanjani ED, et al. Measurement of marrow repopulating potential of human hematopoietic progenitor and stem cells using a fetal sheep model. Prog Clin Biol Res JT-Progress in clinical and biological research, 1994,389:281-291.
[63]Datta S. Activation of neuroblast proliferation in explant culture of the Drosophila larval CNS. Brain Res JT-Brain research,1999,818(1):77-83.
[64]Donnelly DS, Krause DS. Hematopoietic stem cells can be CD34+ or CD34-Leuk Lymphoma JT-Leukemia & lymphoma,2001,40(3-4):221-234.
[65]Chiu RC, Zibaitis A, Kao RL. Cellular cardiomyoplasty:myocardial regeneration with satellite cell implantation. Ann Thorac Surg JT-The Annals of thoracic surgery, 1995,60(1):12-18.
[66]Friedenstein AJ, Chailakhyan RK, Gerasimov UV. Bone marrow osteogenic stem cells:in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet JT-Cell and tissue kinetics,1987,20(3):263-272.
[67]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science JT-Science,1999,284(5411):143-147.
[68]Healy L, May G, Gale K, et al. The stem cell antigen CD34 functions as a regulator of hemopoietic cell adhesion. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America, 1995,92(26):12240-12244.
[69]Titley I, Healy LE, Scott M, et al. Extent of variability inherent in measurements of CD34-positive cells in different human haemopoietic tissues. Bone Marrow Transplant JT-Bone marrow transplantation,1995,16(4):611-616.
[70]Pereira RF, Halford KW, O'Hara MD, et al. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc Natl Acad Sci U S A JT-Proceedings of the National Academy of Sciences of the United States of America,1995,92(11):4857-4861.
[71]Lee JH, Kosinski PA, Kemp DM. Contribution of human bone marrow stem cells to individual skeletal myotubes followed by myogenic gene activation. Exp Cell Res JT-Experimental cell research,2005,307(1):174-182.
[72]Alexanian AR. Neural stem cells induce bone-marrow-derived mesenchymal stem cells to generate neural stem-like cells via juxtacrine and paracrine interactions. Exp Cell Res JT-Experimental cell research,2005,310(2):383-391.
[73]Kashofer K, Bonnet D. Gene therapy progress and prospects:stem cell plasticity. Gene Ther JT-Gene therapy,2005,12(16):1229-1234.
[74]Phinney DG, Isakova I. Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des JT-Current pharmaceutical design, 2005,11(10):1255-1265.
[75]Wislet-Gendebien S, Hans G, Leprince P, et al. Plasticity of cultured mesenchymal stem cells:switch from nestin-positive to excitable neuron-like phenotype. Stem Cells JT-Stem cells (Dayton, Ohio),2005,23(3):392-402.
[76]Phinney DG, Kopen G, Isaacson RL, et al. Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice:variations in yield, growth, and differentiation. J Cell Biochem JT-Journal of cellular biochemistry, 1999,72(4):570-585.
[77]Aubin JE. Bone stem cells. J Cell Biochem Suppl JT-Journal of cellular biochemistry. Supplement,1998,30-31:73-82.
[78]Thomas T, Gori F, Spelsberg TC, et al. Response of bipotential human marrow stromal cells to insulin-like growth factors:effect on binding protein production, proliferation, and commitment to osteoblasts and adipocytes. Endocrinology JT-Endocrinology,1999,140(11):5036-5044.
[79]Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology JT-Endocrinology,1999,140(4):1630-1638.
[80]Schoeberlein A, Holzgreve W, Dudler L, et al. Tissue-specific engraftment after in utero transplantation of allogeneic mesenchymal stem cells into sheep fetuses. Am J Obstet Gynecol JT-American journal of obstetrics and gynecology, 2005,192(4):1044-1052.
[81]Airey JA, Almeida-Porada G, Colletti EJ, et al. Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart. Circulation JT-Circulation, 2004,109(11):1401-1407.
[82]Digirolamo CM, Stokes D, Colter D, et al. Propagation and senescence of human marrow stromal cells in culture:a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol JT-British journal of haematology,1999,107(2):275-281.
[83]Young HE, Steele TA, Bray RA, et al. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec JT-The Anatomical record, 2001,264(1):51-62.
[84]Deans RJ, Moseley AB. Mesenchymal stem cells:biology and potential clinical uses. Exp Hematol JT-Experimental hematology,2000,28(8):875-884.
[85]Guerriero A, Worford L, Holland HK, et al. Thrombopoietin is synthesized by bone marrow stromal cells. Blood JT-Blood,1997,90(9):3444-3455.
[86]Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science JT-Science,1997,276(5309):71-74.
[87]Wilson SE, He YG, Weng J, et al. Effect of epidermal growth factor, hepatocyte growth factor, and keratinocyte growth factor, on proliferation, motility and differentiation of human corneal epithelial cells. Exp Eye Res JT-Experimental eye research,1994,59(6):665-678.
[88]Crosbie OM, Reynolds M, McEntee G, et al. In vitro evidence for the presence of hematopoietic stem cells in the adult human liver. Hepatology JT-Hepatology (Baltimore, Md.),1999,29(4):1193-1198.
[89]Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science JT-Science,1999,284(5417):1168-1170.
[90]Liu J, Xue L. [The regulatory mechanism of liver oval cell differentiation.]. Zhonghua Gan Zang Bing Za Zhi,2005,13(12):951-953.
[91]Ichiba M, Shimomura T, Murai R, et al. Dual effects of adenovirus-mediated thrombopoietin gene transfer on hepatic oval cell proliferation and platelet counts. Biochem Biophys Res Commun JT-Biochemical and biophysical research communications,2005,335(3):723-729.
[92]Jeong WI, Jeong DH, Do SH, et al. Expression of cytokeratins 8 and 18 on Mallory body and oval cell in rats during hepatic fibrosis. In Vivo JT-In vivo (Athens, Greece),2005,19(4):769-775.
[93]Lazaro CA, Rhim JA, Yamada Y, et al. Generation of hepatocytes from oval cell precursors in culture. Cancer Res JT-Cancer research,1998,58(23):5514-5522.
[94]Pi L, Oh SH, Shupe T, et al. Role of connective tissue growth factor in oval cell response during liver regeneration after 2-AAF/PHx in rats. Gastroenterology JT-Gastroenterology,2005,128(7):2077-2088.
[95]Subrata LS, Lowes KN, Olynyk JK, et al. Hepatic expression of the tumor necrosis factor family member lymphotoxin-beta is regulated by interleukin (IL)-6 and IL-lbeta:transcriptional control mechanisms in oval cells and hepatoma cell lines. Liver Int JT-Liver international:official journal of the International Association for the Study of the Liver,2005,25(3):633-646.
[96]Kofman AV, Morgan G, Kirschenbaum A, et al. Dose-and time-dependent oval cell reaction in acetaminophen-induced murine liver injury. Hepatology JT Hepatology (Baltimore, Md.),2005,41(6):1252-1261.
[97]Brooling JT, Campbell JS, Mitchell C, et al. Differential regulation of rodent hepatocyte and oval cell proliferation by interferon gamma. Hepatology JT Hepatology (Baltimore, Md.),2005,41(4):906-915.
[98]Zajicek G, Oren R, Weinreb M Jr. The streaming liver. Liver JT-Liver, 1985,5(6):293-300.
[99]Forbes SJ, Themis M, Alison MR, et al. Synergistic growth factors enhance rat liver proliferation and enable retroviral gene transfer via a peripheral vein. Gastroenterology JT-Gastroenterology,2000,118(3):591-598.
[100]Werlich T, Stiller KJ, Machnik G. Experimental studies on the stem cell concept of liver regeneration. Ⅱ. Exp Toxicol Pathol JT-Experimental and toxicologic pathology:official journal of the Gesellschaft fur Toxikologische Pathologie,1999,51(1):93-98.
[101]Preisegger KH, Factor VM, Fuchsbichler A, et al. Atypical ductular proliferation and its inhibition by transforming growth factor betal in the 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse model for chronic alcoholic liver disease. Lab Invest JT-Laboratory investigation; a journal of technical methods and pathology,1999,79(2):103-109.
[102]Lemire JM, Shiojiri N, Fausto N. Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine. Am J Pathol JT-The American journal of pathology,1991,139(3):535-552.
[103]Shiojiri N, Lemire JM, Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Res JT-Cancer research,1991,51(10):2611-2620.
[104]Cubero FJ, Maganto P, Mula N, et al. Hepatic proliferation in Gunn rats transplanted with hepatocytes:effect of retrorsine and tri-iodothyronine. Cell Prolif JT-Cell proliferation,2009,38(3):137-146.
[105]Dahlke MH, Popp FC, Bahlmann FH, et al. Liver regeneration in a retrorsine/CCl4-induced acute liver failure model:do bone marrow-derived cells contribute?. J Hepatol JT-Journal of hepatology,2009,39(3):365-373.
[106]Cereghini S. Liver-enriched transcription factors and hepatocyte differentiation. FASEB J JT-The FASEB journal:official publication of the Federation of American Societies for Experimental Biology,1996,10(2):267-282.
[107]Lazennec G, Kern L, Valotaire Y, et al. The nuclear orphan receptors COUP-TF and ARP-1 positively regulate the trout estrogen receptor gene through enhancing autoregulation. Mol Cell Biol JT-Molecular and cellular biology, 1997,17(9):5053-5066.
[108]Tanaka T, Yoshida N, Kishimoto T, et al. Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO J JT-The EMBO journal,1997,16(24):7432-43.
[109]Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature JT-Nature,2009,406(6793):257.
[110]Kim TH, Mars WM, Stolz DB, et al. Extracellular matrix remodeling at the early stages of liver regeneration in the rat. Hepatology JT-Hepatology (Baltimore, Md.),2009,26(4):896-904.
[111]Yin L, Ghebranious N, Chakraborty S, et al. Control of mouse hepatocyte proliferation and ploidy by p53 and p53ser246 mutation in vivo. Hepatology JT-Hepatology (Baltimore, Md.),2008,27(1):73-80.
[112]Najimi M, Sokal E. Liver cell transplantation. Minerva Pediatr JT Minerva pediatrica,2009,57(5):243-257.
[1]Pertersen BE. Hepatic"stem"cells:coming full circle[J]. B loodcellsMol D is, 2001,27 (3):590.
[2]BeschornerWE, Civin CI, StraussLC. Localization of hematopoi2etic p rogenitor cells in tissue with the anti2My210 monoclonal anti2body[J]. Am J Pathol,1985, 119(1):1-4.
[3]Radaeva (Pronina) SA, Faktor VM. The differentiation of ovalcells into hepartocytes during induced hepatic carcinogenesis inmice. An electron microscop ic study [J]. Tsitologiia,1990,32 (4):331-336.
[4]FaktorVM, Radaeva SA. The formation of oval2cell ducts duringhepatic carcinogenesis in mice. Its relationship to the p re2exitingcanals of Hering[J]. Ontogenez,1992,23 (4):407-418.
[5]Kennedy S, Rettinger S, Flye MW, et al. Experiments in trans2genic mice show that hepatocytes are the source for postnatal livergrowth and do not stream[J]. Hepatology,1995,22:160-168.
[6]Burke ZD, Shen CN, Ralphs KL, et al. Characterization of liverfunction in transdifferentiated hepatocytes [J]. J Cell Physiol,2006,206 (1):147-159.
[7]Petersen BE, BowenWC, Patrene KD, et al. Bone marrow as apotential source of hepatic oval cells[J]. Science,1999,284:1168-1170.
[8]GrompeM. The role of bone marrow stem cells in liver regenera2tion[J]. Sem in L iverD is,2003,23 (4):363-372.
[9]Oh SH, Witek RP, Bae SH, et al. Bone marrow2derived hepaticoval cells differentiate into hepatocytes in 22acetylaminofluorene/partial hepatectomy2induced liver regeneration[J]. Gastroenterology,2007,132 (3):1077-1087.
[10]Wang X, FosterMA, A12Dhalimym, et al. The origin and liver re2population capacity of murine oval cells [J]. Proc N atl Acad Sci USA,2003,100:11881 11888.
[11]Szabo E, Lodi C, Korpos E, et al. Exp ression ofmatrilin22 in ovalcells during rat liver regeneration[J]. Matrix B iol,2007,21.
[12]YovchevMI, Grozdanov PN, Joseph B, et al. Novel hepatic p ro2genitor cell surface markers in the adult rat liver[J]. Hepatology,2007,45 (1):139-149.
[13]Grozdanov PN, YovchevMI, Dabeva MD. The oncofetal p roteinglyp ican23 is a novelmarker of hepatic p rogenitor/oval cells[J]. Lab Invest,2006,86 (12):1272-1284.
[14]SoltDB, Cayama E, Tsuda H, et al. Promotion of liver cancer de2velopment by brief exposure to dietary 22acetylaminofluorene p luspartial hepatectomy or carbon tetrachloride [J]. Cacer Res,1983,43 (1):188-191.
[15]Ise N, Sato T, Yasui O, et al. Enhanced p roliferation of hepaticp rogenitor cells in rats after portal branch occlusion [J]. Liver Transpl,2004,10 (6):748-754.
[16]SuzukiA, Zheng YW, Kondo R, et al. Flow2cytometric separationand enrichment of hepatic p rogenitor cells in the develop ingmouseliver[J]. J Hepatology,2000,32 (6):1230-1239.
[17]Gordon GJ, Butz GM, Grisham JW, et al. Isolation short2termculture and transp lantation of small hepatocyte21ike p rogenitor cellsfrom retrorisine2exposed rats[J]. J Transplantation,2002,73 (8):1236-1243.
[18]王宇明,陈耀凯,郎松等。大鼠肝卵圆细胞的分离培养及脾内移植研究[J].中华肝脏病杂志,2003,6(11)：328-330.
[19]Nakauchi H. Isolation and clonal characterization of hematopoieticand liver stem cells[J]. Cornea,2004,23 (8 Supp 1):S2-7.
[20]Stamp L, Crosby HA, Hawes SM, et al. A novel cell2surfacemarker found on human embryonic hepatoblasts and a subpopulation of hepatic biliary ep ithelial cells [J]. S tem Cells,2005,23 (1):103-112.
[21]Monga SP, Tang Y, Candotti F, et al. Exapansion of hepatic andhematopoietic stem cells utilizing mouse embryonic liver exp lants [J]. Cell Transplant,2001,10 (1):81-89.
[22]Zheng D, Oh SH, Jung Y, Petersen BE. Oval cell response in 22acetylamino-fluorene/partial hepatectomy rat is attenuated by shortinterfering RNA targeted to stromal cell2derived factor21 [J]. Am JPathol,2006,169 (6):2066-2074.
[23]Piscaglia AC, Shupe TD, Oh SH, et al. Granulocyte2colony stimulating factor p romotes liver repair and induces oval cell migrationand p roliferation in rats[J]. Gastroenterology,2007,133 (2):619-631.
[24]Suzuki A, Zheng YW, Fukao K, et al. Hepatic stem/p rogenitorcellswith high p roliferative potential in liver organ formation [J]. Transplantation Proceeding,2001, 33:585-586.
[25]He ZP, TanWQ, Tanq YF, et al. Activation isolation identifica2tion and in vitro p roliferation of oval cells from adult rat livers[J]. Cell Prolif,2004,37 (2):177-187.
[26]Chen JZ, Hong H, Xiang J, et al. A selective trop ism of transfused oval cells for liver[J]. World J Gastroenterol,2003,9:544-546.
[27]Machi H, Irani AN, Gagandeep S, et al. Isolation of human p rogenitor liver ep ithelial cellswith extensive rep lication capacity and differentiation into mature hepatocytes[J]. J Cell Sci,2002,115 (10):2679.
[28]薛玲,廖冰,赵国强,等,大鼠肝癌形成过程中癌基因表达变化的意义[J].世界华人消化杂志,2003,11：904-907.
[29]DumbleML, Croager EJ, Yeoh GC. Generation and characterization of p53 null transformed hepatic p rogenitor cells, oval cellsgive rise tohepatocellular carcinoma [J]. Carcinogenesis,2002,23:435-445.
[30]TsamandasAC, Syrokosta I, Thomopoulos K, et al. Potential role of hepatic p rogenitor cells exp ression in cases of chronic hepatitis Cand their relation to response to theropy:a clinicopathop logic study [J]. L iver Int,2006,26 (7):817-826.
[31]Katoonizadeh A, Nevens F, Verslype C, et al. Liver regeneration in acute severe liver impairment:a clinicopathological correlation study[J]. L iver Int,2006,26 (10): 1225-1233.
[32]KusanoM, MitoM. Observations on the fine structure of ling survived hepatocytes inoculated into rat sp leen[J]. Gastroenterology,1982,82:616-628.
[33]Avital I, Feraresso C, Aoki T, et al. Bone marrow2derival liver stem cell and mature hepatocyte engraftment in livers undergoing rejection[J]. Surgery,2000,132: 384-390.
[34]Matsusaka S, Toyosaka A, Nakasho K, et al. The role of oval cells in rat hepaticyte transp lantation[J]. Transplation,2000,70:441-446.
[35]Fang B, ShiM, Liao L, et al. Systemic infusion of FLKI (+) mesenchymal stem cells ameliorate carbon tetrachloride2induced liver fibrosis in mice[J]. Transplation, 2004,78 (1):83-88.
[36]Yu Y, Yao AH, Chen N, et al. Mesenchymal stem cells over exp ressing hepatocyte growth factor imp rove small2for2size liver graftsregeneration[J]. M ol Ther,2007:22.
[37]姚鹏,胡大荣,王帅等。人自体骨髓干细胞移植治疗慢性肝功能衰竭的研究[J].中华肝脏病杂志,2005,13：941-942。
[38]Gupa DK, Sharma S, Venugopal P, et al. Transp lant Proc,2007Ap r; 39 (3): 700-702.