人鼠嵌合肝研究进展
林沪, 毛青, 王宇明, 中国人民解放军第三军医大学西南医院感染病研究所 重庆市 400038
林沪, 男,1970-01-08, 重庆市人, 汉族. 1993大学本科毕业, 中级职称, 主要从事肝病方面研究.
通讯作者: 林沪, 400038, 重庆市沙坪坝区高滩岩正街30号, 中国人民解放军第三军医大学西南医院感染病研究所. linhu7018@yahoo.com.cn
电话: 023-65399064 传真: 023-68754475
收稿日期: 2005-04-15 接受日期: 2005-04-27
摘要
, 百拇医药
人鼠嵌合肝动物模型的建立可为进一步研究病毒性、代谢性肝病的发病机制、治疗药物及疫苗开发提供新的技术手段，具有良好的前景与发展意义.本文综述了人鼠嵌合肝相关内容，包括该模型建立原理、移植细胞来源、建立途径与方法，介绍了近期研究进展，探讨了如何进一步提高移植细胞的增殖能力以延长生存时间这一重要课题.
关键词: 人鼠嵌合肝
林沪,毛青,王宇明.人鼠嵌合肝研究进展.世界华人消化杂志 2005;13(12):1373-1376
Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, Addison WR, Fischer KP, Churchill TA, Lakey JR, Tyrrell
DL, Kneteman NM. Hepatitis C virus replication in mice with chimeric human livers. Nat Med 2001;7:927-933
, 百拇医药
2 Wu CH, Ouyang EC, Walton CM, Wu GY. Human hepatocytes transplanted into genetically immunocompetent
rats are susceptible to infection by hepatitis B virus in situ. J Viral Hepat 2001;8:111-119
3 Dandri M, Burda MR, Torok E, Pollok JM, Iwanska A, Sommer G, Rogiers X, Rogler CE, Gupta S, Will H, Greten H,Petersen J. Repopulation of mouse liver with human hepatocytes and In vivo infection with hepatitis B virus.
, 百拇医药
Hepatology 2001;33:981-988
4 Brass V, Blum HE, Moradpour D. Of mice and men: a small animal model of hepatitis C virus replication.
Hepatology 2002;35:722-724
5 Zhu Y, Yamamoto T, Cullen J, Saputelli J, Aldrich CE, Miller DS, Litwin S, Furman PA, Jilbert AR, Mason WS.
Kinetics of Hepadnavirus loss from the liver during inhibition of viral DNA synthesis. J Virol 2001;75:311-322
, http://www.100md.com
6 Wu CH, Ouyang EC, Walton C, Wu GY. Liver cell transplantation-novel animal model for human hepatic viral
infections. Croat Med J 2001;42:446-450
7 Ouyang EC, Wu CH, Walton C, Promrat K, Wu GY. Transplantation of human hepatocytes into tolerized
genetically immunocompetent rats. World J Gastroenterol 2001;7:324-330
8 蒋黎, 毛青, 王宇明, 李俊刚, 刘俊. HBV感染的人鼠嵌合肝动物模型的建立. 第三军医大学学报 2003;25:38
, 百拇医药
9 周晓东, 佘丽君. 肝细胞移植的细胞来源与适应证. 中华肝病杂志 2003;11:368
10 Shafritz DA, Dabeva MD. Liver stem cells and model systems for liver repopulation. J Hepatol 2002;36:552-564
11 Di Campli C, Nestola M, Piscaglia AC, Santoliquido A, Gasbarrini G, Pola P, Gasbarrini A. Cell-based therapy
for liver diseases. Eur Rev Med Pharmacol Sci 2003;7:41-44
12 Fandrich F, Ruhnke M. Stem cells and liver replacement. Med Klin (Munich) 2003;98(Suppl 2):18-22
, 百拇医药
13 Mikula M, Fuchs E, Huber H, Beug H, Schulte-Hermann R, Mikulits W. Immortalized p19ARF null
hepatocytes restore liver injury and generate hepatic progenitors after transplantation. Hepatology 2004;39:628-634
14 Gupta S, Lee CD, Vemuru RP, Bhargava KK. 111Indium labeling of hepatocytes for analysis of short-term
biodistribution of transplanted cells. Hepatology 1994;19:750-757
, 百拇医药
15 Selden C, Hodgson H. Cellular therapies for liver replacement. Transpl Immunol 2004;12:273-288
16 姜涛, 张雪林. 经脾肝细胞移植的研究进展. 肝脏 2003;8:56-59
17 Wu CH, Ouyang EC, Walton C, Promrat K, Forouhar F, Wu GY. Hepatitis B virus infection of transplanted
human hepatocytes causes a biochemical and histological hepatitis in immunocompetent rats. World J
Gastroenterol 2003;9:978-983
, 百拇医药
18 Rajvanshi P, Kerr A, Bhargava KK, Burk RD, Gupta S. Efficacy and safety of repeated hepatocyte transplantation
for significant liver repopulation in rodents. Gastroenterology 1999;111:1092-1102
19 Guha C, Deb NJ, Sappal BS, Ghosh SS, Roy-Chowdhury N, Roy-Chowdhury J. Amplification of engrafted hepatocytes
by preparative manipulation of the host liver. Artif Organs 2001;25:522-528
, 百拇医药
20 Witek RP, Fisher SH, Petersen BE. Monocrotaline, an alternative to retrorsine-based hepatocyte transplantation
in rodents. Cell Transplant 2005;14:41-47
21 Laconi E, Laconi S. Principles of hepatocyte repopulation. Semin Cell Dev Biol 2002;13:433-438
22 Koenig S, Stoesser C, Krause P, Becker H, Markus PM. Liver repopulation after hepatocellular
, 百拇医药 transplantation: integration and interaction of transplanted hepatocytes in the host. Cell Transplant
2005;14:31-40
23 Laconi S, Pillai S, Porcu PP, Shafritz DA, Pani P, Laconi E. Massive liver replacement by transplanted hepatocytes
in the absence of exogenous growth stimuli in rats treated with retrorsine. Am J Pathol 2001;158:771-777
24 Oertel M, Rosencrantz R, Chen YQ, Thota PN, Sandhu JS, Dabeva MD, Pacchia AL, Adelson ME, Dougherty JP, Shafritz
, http://www.100md.com
DA. Repopulation of rat liver by fetal hepatoblasts and adult hepatocytes transduced ex vivo with lentiviral
vectors. Hepatology 2003;37:994-1005
25 Dabeva MD, Shafritz DA. Hepatic stem cells and liver repopulation. Semin Liver Dis 2003;23:349-362
26 Sandhu JS, Petkov PM, Dabeva MD, Shafritz DA. Stem cell properties and repopulation of the rat liver
, http://www.100md.com by fetal liver epithelial progenitor cells. Am J Pathol 2001;159:1323-1334
27 Wang X, Montini E, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. Kinetics of liver repopulation after bone
marrow transplantation. Am J Pathol 2002;161:565-574
28 Di Campli C, Piscaglia AC, Pierelli L, Rutella S, Bonanno G, Alison MR, Mariotti A, Vecchio FM, Nestola M, Monego
G, Michetti F, Mancuso S, Pola P, Leone G, Gasbarrini G, Gasbarrini A. A human umbilical cord stem cell rescue
therapy in a murine model of toxic liver injury. Dig Liver Dis 2004;36:603-613
编辑 王谨晖 审读 张海宁, 百拇医药( 林 沪, 毛 青, 王宇明)
林沪, 男,1970-01-08, 重庆市人, 汉族. 1993大学本科毕业, 中级职称, 主要从事肝病方面研究.
通讯作者: 林沪, 400038, 重庆市沙坪坝区高滩岩正街30号, 中国人民解放军第三军医大学西南医院感染病研究所. linhu7018@yahoo.com.cn
电话: 023-65399064 传真: 023-68754475
收稿日期: 2005-04-15 接受日期: 2005-04-27
摘要
, 百拇医药
人鼠嵌合肝动物模型的建立可为进一步研究病毒性、代谢性肝病的发病机制、治疗药物及疫苗开发提供新的技术手段，具有良好的前景与发展意义.本文综述了人鼠嵌合肝相关内容，包括该模型建立原理、移植细胞来源、建立途径与方法，介绍了近期研究进展，探讨了如何进一步提高移植细胞的增殖能力以延长生存时间这一重要课题.
关键词: 人鼠嵌合肝
林沪,毛青,王宇明.人鼠嵌合肝研究进展.世界华人消化杂志 2005;13(12):1373-1376
Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, Addison WR, Fischer KP, Churchill TA, Lakey JR, Tyrrell
DL, Kneteman NM. Hepatitis C virus replication in mice with chimeric human livers. Nat Med 2001;7:927-933
, 百拇医药
2 Wu CH, Ouyang EC, Walton CM, Wu GY. Human hepatocytes transplanted into genetically immunocompetent
rats are susceptible to infection by hepatitis B virus in situ. J Viral Hepat 2001;8:111-119
3 Dandri M, Burda MR, Torok E, Pollok JM, Iwanska A, Sommer G, Rogiers X, Rogler CE, Gupta S, Will H, Greten H,Petersen J. Repopulation of mouse liver with human hepatocytes and In vivo infection with hepatitis B virus.
, 百拇医药
Hepatology 2001;33:981-988
4 Brass V, Blum HE, Moradpour D. Of mice and men: a small animal model of hepatitis C virus replication.
Hepatology 2002;35:722-724
5 Zhu Y, Yamamoto T, Cullen J, Saputelli J, Aldrich CE, Miller DS, Litwin S, Furman PA, Jilbert AR, Mason WS.
Kinetics of Hepadnavirus loss from the liver during inhibition of viral DNA synthesis. J Virol 2001;75:311-322
, http://www.100md.com
6 Wu CH, Ouyang EC, Walton C, Wu GY. Liver cell transplantation-novel animal model for human hepatic viral
infections. Croat Med J 2001;42:446-450
7 Ouyang EC, Wu CH, Walton C, Promrat K, Wu GY. Transplantation of human hepatocytes into tolerized
genetically immunocompetent rats. World J Gastroenterol 2001;7:324-330
8 蒋黎, 毛青, 王宇明, 李俊刚, 刘俊. HBV感染的人鼠嵌合肝动物模型的建立. 第三军医大学学报 2003;25:38
, 百拇医药
9 周晓东, 佘丽君. 肝细胞移植的细胞来源与适应证. 中华肝病杂志 2003;11:368
10 Shafritz DA, Dabeva MD. Liver stem cells and model systems for liver repopulation. J Hepatol 2002;36:552-564
11 Di Campli C, Nestola M, Piscaglia AC, Santoliquido A, Gasbarrini G, Pola P, Gasbarrini A. Cell-based therapy
for liver diseases. Eur Rev Med Pharmacol Sci 2003;7:41-44
12 Fandrich F, Ruhnke M. Stem cells and liver replacement. Med Klin (Munich) 2003;98(Suppl 2):18-22
, 百拇医药
13 Mikula M, Fuchs E, Huber H, Beug H, Schulte-Hermann R, Mikulits W. Immortalized p19ARF null
hepatocytes restore liver injury and generate hepatic progenitors after transplantation. Hepatology 2004;39:628-634
14 Gupta S, Lee CD, Vemuru RP, Bhargava KK. 111Indium labeling of hepatocytes for analysis of short-term
biodistribution of transplanted cells. Hepatology 1994;19:750-757
, 百拇医药
15 Selden C, Hodgson H. Cellular therapies for liver replacement. Transpl Immunol 2004;12:273-288
16 姜涛, 张雪林. 经脾肝细胞移植的研究进展. 肝脏 2003;8:56-59
17 Wu CH, Ouyang EC, Walton C, Promrat K, Forouhar F, Wu GY. Hepatitis B virus infection of transplanted
human hepatocytes causes a biochemical and histological hepatitis in immunocompetent rats. World J
Gastroenterol 2003;9:978-983
, 百拇医药
18 Rajvanshi P, Kerr A, Bhargava KK, Burk RD, Gupta S. Efficacy and safety of repeated hepatocyte transplantation
for significant liver repopulation in rodents. Gastroenterology 1999;111:1092-1102
19 Guha C, Deb NJ, Sappal BS, Ghosh SS, Roy-Chowdhury N, Roy-Chowdhury J. Amplification of engrafted hepatocytes
by preparative manipulation of the host liver. Artif Organs 2001;25:522-528
, 百拇医药
20 Witek RP, Fisher SH, Petersen BE. Monocrotaline, an alternative to retrorsine-based hepatocyte transplantation
in rodents. Cell Transplant 2005;14:41-47
21 Laconi E, Laconi S. Principles of hepatocyte repopulation. Semin Cell Dev Biol 2002;13:433-438
22 Koenig S, Stoesser C, Krause P, Becker H, Markus PM. Liver repopulation after hepatocellular
, 百拇医药 transplantation: integration and interaction of transplanted hepatocytes in the host. Cell Transplant
2005;14:31-40
23 Laconi S, Pillai S, Porcu PP, Shafritz DA, Pani P, Laconi E. Massive liver replacement by transplanted hepatocytes
in the absence of exogenous growth stimuli in rats treated with retrorsine. Am J Pathol 2001;158:771-777
24 Oertel M, Rosencrantz R, Chen YQ, Thota PN, Sandhu JS, Dabeva MD, Pacchia AL, Adelson ME, Dougherty JP, Shafritz
, http://www.100md.com
DA. Repopulation of rat liver by fetal hepatoblasts and adult hepatocytes transduced ex vivo with lentiviral
vectors. Hepatology 2003;37:994-1005
25 Dabeva MD, Shafritz DA. Hepatic stem cells and liver repopulation. Semin Liver Dis 2003;23:349-362
26 Sandhu JS, Petkov PM, Dabeva MD, Shafritz DA. Stem cell properties and repopulation of the rat liver
, http://www.100md.com by fetal liver epithelial progenitor cells. Am J Pathol 2001;159:1323-1334
27 Wang X, Montini E, Al-Dhalimy M, Lagasse E, Finegold M, Grompe M. Kinetics of liver repopulation after bone
marrow transplantation. Am J Pathol 2002;161:565-574
28 Di Campli C, Piscaglia AC, Pierelli L, Rutella S, Bonanno G, Alison MR, Mariotti A, Vecchio FM, Nestola M, Monego
G, Michetti F, Mancuso S, Pola P, Leone G, Gasbarrini G, Gasbarrini A. A human umbilical cord stem cell rescue
therapy in a murine model of toxic liver injury. Dig Liver Dis 2004;36:603-613
编辑 王谨晖 审读 张海宁, 百拇医药( 林 沪, 毛 青, 王宇明)
