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OALib Journal期刊
ISSN: 2333-9721
费用：99美元
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人成体肝细胞在Fah-/-Nod/Scid小鼠肝脏中的显著增殖
, PP. 929-937
苏宝亮, 刘长城, 向导, 张海斌, 袁斯明, 王敏君, 陈费, 朱海英, 何志颖, 王欣, 胡以平
Keywords: 人肝细胞,人源化肝脏,细胞移植,Fah基因剔除小鼠,Nod/Scid小鼠
Abstract:
利用人肝细胞异种移植到受体鼠肝内建立人源化肝脏的嵌合体小鼠(人鼠嵌合肝)对药物代谢、乙型肝炎病毒等嗜肝性病毒及其疫苗的研究具有重要意义.研究表明,利用Fah-/-Rag2-/-Il2rg-/-三基因剔除小鼠可获得人肝细胞在小鼠肝脏中的显著再殖,但较高的死亡率及纯合子不能用于繁殖,制约着该小鼠模型的规模化应用.本研究结合延胡索酰乙酰乙酸水解酶基因剔除(Fah-/-)小鼠的肝脏再殖优势和Nod/Scid小鼠异种移植的特点,将这两种小鼠进行杂交繁育建立Fah-/-Nod/Scid小鼠品系,Fah-/-Nod/Scid小鼠可以纯合保种并能正常繁殖.采用提前停药的预处理方案,结合FK506处理,移植的人成体肝细胞能够实现在Fah-/-Nod/Scid小鼠肝脏中的显著增殖,肝脏再殖程度达到30%以上.采用体重曲线、肝功能和人肝细胞功能蛋白表达等三方面指标评价嵌合肝脏中人肝细胞的功能,结果表明再殖的肝细胞具有正常的人肝细胞功能.这些结果表明,Fah-/-Nod/Scid小鼠可以作为理想的可规模应用的人鼠嵌合肝模型,该技术体系的改进简化了Fah-/-小鼠作为人源化肝脏小鼠模型的实用性问题.
| [1] | 1 Meuleman P, Libbrecht L, De Vos R, et al. Morphological and biochemical characterization of a human liver in an uPA-SCID mouse
|
| [2] | chimera. Hepatology, 2005, 41: 847—856
|
| [3] | 5 Sugiyama M, Tanaka Y, Kurbanov F, et al. Direct cytopathic effects of particular hepatitis B virus genotypes in severe combined
|
| [4] | immunodeficiency transgenic with urokinase-type plasminogen activator mouse with human hepatocytes. Gastroenterology, 2009, 136: 652—
|
| [5] | 574
|
| [6] | 13 Wang X, Foster M, Al-Dhalimy M, et al. The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci USA, 2003,
|
| [7] | 100(S1): 11881—11888
|
| [8] | 14 Shultz L D, Schweitzer P A, Christianson S W, et al. Multiple defects of innate and adaptive immunologic function in NOD/LtSz-scid mice.
|
| [9] | J Immunol, 1995, 154: 180—191
|
| [10] | 15 Wilber A, Wangensteen K J, Chen Y, et al. Messenger RNA as a source of transposase for sleeping beauty transposon-mediated correction
|
| [11] | of hereditary tyrosinemia type I. Mol Ther, 2007, 15: 1280—1287
|
| [12] | 16 Tateno C, Yoshizane Y, Saito N, et al. Near completely humanized liver in mice shows human-type metabolic responses to drugs. Am J
|
| [13] | Pathol, 2004, 165: 901—912
|
| [14] | 17 Rhim J A, Sandgren E P, Degen J L, et al. Replacement of diseased mouse liver by hepatic cell transplantation. Science, 1994, 263: 1149—
|
| [15] | 1152
|
| [16] | 18 Escribano O, Fernández-Moreno M D, Pi？a M J, et al. Pretreatment with FK506 up-regulates insulin receptors in regenerating rat liver.
|
| [17] | Hepatology, 2002, 36: 555—561
|
| [18] | 19 Kawamura I, Takeshita S, Fushimi M, et al. Induction of choleresis by inmunosuppressant FK506 through stimulation of insulin-like growth
|
| [19] | factor I production in the liver of rats. Eur J Pharmacol, 2001, 419: 99—105
|
| [20] | 20 Tanaka N, Yamamoto H, Tatemoto A, et al. Regulation of liver regeneration by interleukin-2 and its inhibitors: cyclosporin A and FK506.
|
| [21] | Int J Immunopharmacol, 1993, 15: 211—218
|
| [22] | 21 Thomale U W, Bender M, Casalis P, et al. Tacrolimus depresses local immune cell infiltration but fails to reduce cortical contusion volume
|
| [23] | in brain-injured rats. Immunobiology, 2007, 212: 567—576
|
| [24] | 22 Setkowicz Z, Caryk M, Szafraniec M, et al. Tacrolimus (FK506) and cyclosporin A reduce macrophage recruitment to the rat brain injured
|
| [25] | at perinatal and early postnatal periods. Neurol Res, 2009, 31: 1060—1067
|
| [26] | 2 Dandri M, Burda M R, T？r？k E, et al. Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus.
|
| [27] | Hepatology, 2001, 33: 981—988
|
| [28] | 3 Mercer D F, Schiller D E, Elliott J F, et al. Hepatitis C virus replication in mice with chimeric human livers. Nat Med, 2001, 7: 927—933
|
| [29] | 4 Vanwolleghem T, Bukh J, Meuleman P, et al. Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human
|
| [30] | liver-chimeric mice from infection with a homologous hepatitis C virus strain. Hepatology, 2008, 47: 1846—1855
|
| [31] | 662. e3
|
| [32] | 6 Dandri M, Murray J M, Lutgehetmann M, et al. Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia.
|
| [33] | Hepatology, 2008, 48: 1079—1086
|
| [34] | 7 Azuma H, Paulk N, Ranade A, et al. Robust expansion of human hepatocytes in Fah？/？/Rag2？/？/Il2rg？/？ mice. Nat Biotechnol, 2007, 25: 903—
|
| [35] | 910
|
| [36] | 8 Bissig K D, Le T T, Woods N B, et al. Repopulation of adult and neonatal mice with human hepatocytes: a chimeric animal model. Proc
|
| [37] | Natl Acad Sci USA, 2007, 104: 20507—20511
|
| [38] | 9 He Z Y, Zhang H B, Zhang X, et al. Liver xeno-repopulation with human hepatocytes in Fah？/？Rag2？/？ mice after pharmacological
|
| [39] | immunosuppression. Am J Pathol, 2010, 177: 1311—1319
|
| [40] | 10 Grompe M, al-Dhalimy M, Finegold M, et al. Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction
|
| [41] | phenotype of lethal albino mice. Genes Dev, 1993, 12: 2298—2307
|
| [42] | 11 Overturf K, al-Dhalimy M, Ou C N, et al. Serial transplantation reveals the stem-cell-like regenerative potential of adult mouse hepatocytes.
|
| [43] | Am J Pathol, 1997, 151: 1273—1280
|
| [44] | 12 Wang X, Montini E, Al-Dhalimy M, et al. Kinetics of liver repopulation after bone marrow transplantation. Am J Pathol, 2002, 161: 565—
|
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