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一种利用产生乙肝表面抗原(HBsAg)的转基因供体细胞进行分离肝细胞移植的新型系统。

A novel system for transplantation of isolated hepatocytes utilizing HBsAg-producing transgenic donor cells.

作者信息

Gupta S, Chowdhury N R, Jagtiani R, Gustin K, Aragona E, Shafritz D A, Chowdhury J R, Burk R D

机构信息

Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.

出版信息

Transplantation. 1990 Sep;50(3):472-5.

PMID:2402796
Abstract

Hepatocytes from donor transgenic mice that produce an easily assayable circulating marker have been used to develop a novel hepatocyte transplantation system. Isolated G7 HBV transgenic donor hepatocytes secreting HBsAg were transplanted into congeneic or allogeneic mouse recipients. Serum HBsAg was present three days after hepatocyte transplantation in congeneic animals and persisted indefinitely when hepatocytes were transplanted into the spleen. Transplanted hepatocytes within the splenic pulp were identified by morphologic and histochemical analysis. Migration of hepatocytes injected into the spleen to the liver was demonstrated by in situ hybridization using an RNA probe for HBsAg. Transplantation into nonimmunosuppressed allogeneic recipients resulted in disappearance of detectable hepatocytes in the spleen within two weeks. This novel transplantation system should facilitate studies of hepatocyte engraftment and survival, modulation of allograft rejection, and development of hepatocyte-directed gene therapy.

摘要

来自产生易于检测的循环标志物的供体转基因小鼠的肝细胞已被用于开发一种新型肝细胞移植系统。将分泌乙肝表面抗原(HBsAg)的分离的G7乙肝病毒(HBV)转基因供体肝细胞移植到同基因或异基因小鼠受体中。在同基因动物中,肝细胞移植后三天血清中出现HBsAg,当肝细胞移植到脾脏中时,HBsAg会无限期持续存在。通过形态学和组织化学分析鉴定脾髓内移植的肝细胞。使用针对HBsAg的RNA探针进行原位杂交证明,注入脾脏的肝细胞向肝脏迁移。移植到未免疫抑制的异基因受体中导致两周内脾脏中可检测到的肝细胞消失。这种新型移植系统应有助于肝细胞植入和存活、同种异体移植排斥调节以及肝细胞定向基因治疗的研究。

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A novel system for transplantation of isolated hepatocytes utilizing HBsAg-producing transgenic donor cells.一种利用产生乙肝表面抗原(HBsAg)的转基因供体细胞进行分离肝细胞移植的新型系统。
Transplantation. 1990 Sep;50(3):472-5.
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Hepatocytes exhibit superior transgene expression after transplantation into liver and spleen compared with peritoneal cavity or dorsal fat pad: implications for hepatic gene therapy.与移植到腹腔或背部脂肪垫相比,肝细胞移植到肝脏和脾脏后表现出更高的转基因表达:对肝脏基因治疗的启示。
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Lamivudine prophylaxis of liver allograft HBV reinfection in HBV related cirrhotic patients after liver transplantation.拉米夫定预防肝移植术后乙肝相关肝硬化患者肝移植肝乙肝病毒再感染
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Hepatocyte transplantation: an alternative system for evaluating cell survival and immunoisolation.肝细胞移植:一种评估细胞存活和免疫隔离的替代系统。
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Can clamping of splenic vessels prevent abrupt increase of portal vein pressure and migration of transplanted hepatocytes to the liver after intrasplenic hepatocyte transplantation?脾血管夹闭能否预防脾内肝细胞移植后门静脉压力的突然升高及移植肝细胞向肝脏的迁移?
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[Intrasplenic transplantation of hepatocytes in spf-ash mice with congenital ornithine transcarbamylase deficiency].[先天性鸟氨酸转氨甲酰酶缺乏的无特定病原体 - 灰小鼠的肝细胞脾内移植]
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引用本文的文献

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Alcoholic liver disease: Utility of animal models.酒精性肝病:动物模型的应用。
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Experimental Model for Successful Liver Cell Therapy by Lenti TTR-YapERT2 Transduced Hepatocytes with Tamoxifen Control of Yap Subcellular Location.通过慢病毒TTR-YapERT2转导的肝细胞并使用他莫昔芬控制Yap亚细胞定位实现成功肝细胞治疗的实验模型
Sci Rep. 2016 Jan 14;6:19275. doi: 10.1038/srep19275.
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Human hepatocyte transplantation: current experience and future challenges.
人肝细胞移植:当前的经验和未来的挑战。
Nat Rev Gastroenterol Hepatol. 2010 May;7(5):288-98. doi: 10.1038/nrgastro.2010.44. Epub 2010 Apr 6.
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Model systems and experimental conditions that lead to effective repopulation of the liver by transplanted cells.能够有效使移植细胞在肝脏中再增殖的模型系统和实验条件。
Int J Biochem Cell Biol. 2011 Feb;43(2):198-213. doi: 10.1016/j.biocel.2010.01.013. Epub 2010 Jan 18.
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ADAMTS13 is expressed in hepatic stellate cells.ADAMTS13在肝星状细胞中表达。
Lab Invest. 2005 Jun;85(6):780-8. doi: 10.1038/labinvest.3700275.
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Transduction of primary rat hepatocytes with bicistronic retroviral vector.用双顺反子逆转录病毒载体转导原代大鼠肝细胞。
World J Gastroenterol. 2000 Oct;6(5):725-729. doi: 10.3748/wjg.v6.i5.725.
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Integration of transplanted hepatocytes into host liver plates demonstrated with dipeptidyl peptidase IV-deficient rats.利用二肽基肽酶IV缺陷大鼠证明移植的肝细胞整合到宿主肝板中。
Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):5860-4. doi: 10.1073/pnas.92.13.5860.
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Mouse hepatocytes migrate to liver parenchyma and function indefinitely after intrasplenic transplantation.小鼠肝细胞在脾内移植后迁移至肝实质并能无限期发挥功能。
Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1217-21. doi: 10.1073/pnas.88.4.1217.
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Transduction of primary human hepatocytes with amphotropic and xenotropic retroviral vectors.用双嗜性和异嗜性逆转录病毒载体转导原代人肝细胞。
Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8981-5. doi: 10.1073/pnas.89.19.8981.