Liver repopulation after cell transplantation in mice treated with retrorsine and carbon tetrachloride1

Guo, Dan‐qing; Fu, Tao; Nelson, Jeffery A.; Superina, Riccardo; Soriano, Humberto E.

doi:10.1097/00007890-200206150-00020

Cited by 72 publications

(60 citation statements)

References 22 publications

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“…Retrorsine and CCl 4 stock solutions were prepared as described previously (Guo et al 2002). Before injection, retrorsine stock solution was diluted 1:5 in sterile PBS.…”

Section: Conditioning Of Recipient Mice and Transplantationmentioning

confidence: 99%

“…All these approaches share the feature that hepatocytes are transplanted into a predamaged liver which provides a regenerative environment for transplanted cells (Shafritz and Dabeva 2002;Dabeva and Shafritz 2003). Recently, Guo et al (2002) reported an enhanced repopulation of the mouse liver after pretreatment of the animals with retrorsine. Retrorsine is an alkaloid that exerts a strong and persistent block of native hepatocyte proliferation (Laconi et al 1999).…”

Section: Intrahepatic Seeding Of Genetically Modified Liver Progenitomentioning

confidence: 99%

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Generation and Analysis of Genetically Defined Liver Carcinomas Derived from Bipotential Liver Progenitors

Zender¹,

Xue²,

Cordon‐Cardo³

et al. 2005

Cold Spring Harbor Symposia on Quantitative Biology

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Hepatocellular carcinoma is a chemoresistant cancer and a leading cause of cancer mortality; however, the molecular mechanisms responsible for the aggressive nature of this disease are poorly understood. In this study, we developed a new liver cancer mouse model that is based on the ex vivo genetic manipulation of embryonic liver progenitor cells (hepatoblasts). After retroviral gene transfer of oncogenes or short hairpin RNAs targeting tumor suppressor genes, genetically altered liver progenitor cells are seeded into the liver of otherwise normal recipient mice. We show that histopathology of the engineered liver carcinomas reveals features of the human disease. Furthermore, representational oligonucleotide microarray analysis (ROMA) of murine liver tumors initiated by two defined genetic hits revealed spontaneously acquired genetic alterations that are characteristic for human hepatocellular carcinoma. This model provides a powerful platform for applications like cancer gene discovery or high-throughput preclinical drug testing.

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“…Retrorsine and CCl 4 stock solutions were prepared as described previously (Guo et al 2002). Before injection, retrorsine stock solution was diluted 1:5 in sterile PBS.…”

Section: Conditioning Of Recipient Mice and Transplantationmentioning

confidence: 99%

Section: Intrahepatic Seeding Of Genetically Modified Liver Progenitomentioning

confidence: 99%

Generation and Analysis of Genetically Defined Liver Carcinomas Derived from Bipotential Liver Progenitors

Zender¹,

Xue²,

Cordon‐Cardo³

et al. 2005

Cold Spring Harbor Symposia on Quantitative Biology

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show abstract

“…Despite a short half life period, retrorsine may suppress hepatocyte proliferation for weeks and even months [24] . Retrorsine mainly blocks phases S and G2 of the liver cell cycle; that is, it blocks cell mitosis.…”

Section: Discussionmentioning

confidence: 99%

Proliferation of L02 human hepatocytes in tolerized genetically immunocompetent rats

Lin

Mao²,

Wang³

et al. 2008

WJG

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AIM:To investigate whether human hepatocytes could proliferate after transplantation to normal immunocompetent rats treated with 2-acetaminofluorene or Retrorsine and partial hepatectomy. METHODS:L02 hepatocyte-tolerant Sprague-Dawley rats were injected with Retrorsine, 2-acetaminofluorene or normal saline. L02 hepatocytes were then transplanted via the spleen. Human albumin and its mRNA, specific proliferating cell nuclear antigen (PCNA), L02 hepatocyte dynamic distribution, number density and area density of PCNA-positive cells in the liver were determined. RESULTS:All the examined indicators were not significantly different between the rats treated with 2-acetaminofluorene and normal saline, which was not the case with rats treated with Retrorsine. A dynamic distribution of L02 hepatocytes in the rat liver was detected from wk 1 to mo 6 after transplantation in the Retrorsine group and from wk 1 to 10 in the 2-acetaminofluorene group. Human albumin and its mRNA were detected from wk 2 to mo 6 in the Retrorsine group and from wk 1 to 8 in the 2-acetaminofluorene group. Specific human PCNA was detected in the rat liver from wk 2 to mo 6 in the Retrorsine group and from wk 2 to 6 in the 2-acetaminofluorene group. Human albumin and its mRNA contents as well as the number of PCNA positive cells reached a peak at wk 4. CONCLUSION:L02 human hepatocytes could not proliferate significiantly after transplantation to the normal, immunocompetent rats treated with 2-acetaminofluorene.L02 human hepatocytes can survive for 10 wk after transplantation and express human albumin for 8 wk. L02 human hepatocytes can proliferate and express human albumin for 6 mo after transplantation to the rats treated with Retrorsine. The chimeric L02 human hepatocytes, which then underwent transplantation into tolerant rats, were normal in morphogenesis, biochemistry and function.

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“…[1][2][3]67,88 To apply this principle to most liver disorders, in which host diseased hepatocytes could compete with donor hepatocytes for liver repopulation, animals were pretreated with retrorsine or subjected to whole liver irradiation to inhibit proliferation ability of host hepatocytes before cell transplantation. 85,89,90 In combination with a strong regenerative pressure (eg twothirds partial hepatectomy, thyroid hormone administration, ischemia-reperfusion injury or FasL gene transfer), a nearly complete repopulation of host liver by donor hepatocytes was obtained after transplantation of 0.5% of the recipient liver mass. 89,[91][92][93] Similarly, lentivirally transduced hepatocytes were massively expanded in retrorsine/partial hepatectomy-treated rats.…”

Section: Strategies For Liver Repopulationmentioning

confidence: 99%

Liver gene therapy: advances and hurdles

Nguyen

Ferry

2004

Gene Ther

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Liver repopulation after cell transplantation in mice treated with retrorsine and carbon tetrachloride1

Cited by 72 publications

References 22 publications

Generation and Analysis of Genetically Defined Liver Carcinomas Derived from Bipotential Liver Progenitors

Generation and Analysis of Genetically Defined Liver Carcinomas Derived from Bipotential Liver Progenitors

Proliferation of L02 human hepatocytes in tolerized genetically immunocompetent rats

Liver gene therapy: advances and hurdles

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