Differentiation of putative hepatic stem cells derived from adult rats into mature hepatocytes in the presence of epidermal growth factor and hepatocyte growth factor

He, Z. P.; Tan, Weiqi; Tang, Yinhe; Feng, Meifu

doi:10.1046/j.1432-0436.2003.7104505.x

Cited by 34 publications

(25 citation statements)

References 22 publications

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“…Moreover, ARF-4-mediated PLD2 activation was required for AP-1-dependent transcription of EGFinduced cellular responses (Kim et al 2003). The EGF was already identified to be necessary for the regenerative response of hepatocytes (Jones et al 1995) but has later been implicated in the proliferation of hepatic oval cells (He et al 2003;Nagy et al 1996). Similar to jun-D, ARFs were weakly expressed in non-parenchymal cells of normal livers and upregulated in non-parenchymal cells and single parenchymal cells after ordinary PH.…”

Section: Discussionmentioning

confidence: 93%

Identification of genes specific to “oval cells” in the rat 2-acetylaminofluorene/partial hepatectomy model

Batusic

Cimica

Chen

et al. 2005

Histochem Cell Biol

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Under certain conditions liver regeneration can be accomplished by hepatic progenitor cells ("oval cells"). So far, only few factors have been identified to be uniquely regulated by the "oval cell" compartment. Using macroarray analysis in a rat model of oval cell proliferation (treatment with 2-acetylaminofluorene and partial hepatectomy, AAF + PH), we identified 12 differentially expressed genes compared to appropriate control models (AAF treatment and sham operation or AAF treatment alone). Further analysis in models of normal liver regeneration (ordinary PH) and acute phase response (turpentine oil-treated rats) revealed that three out of 12 genes (thymidine kinase 1, Jun-D and ADP-ribosylation factor 4) were not affected by the hepatic acute phase reaction but similarly overexpressed in both "oval cell"-dependant and normal liver regeneration. We characterized Jun-D and ADP-ribosylation factors as novel factors upregulated in oval cells and in non-parenchymal liver cells of normally regenerating livers. However, two out of 12 differentially expressed genes were specifically expressed in oval cells: ras-related protein Rab-3b and Ear-2. On protein level, Rab-3b was increased in total liver homogenates and demonstrated only in clusters of oval cells. We postulate that Ear-2 and Rab-3b may represent novel regulatory factors specifically activated in "oval cells".

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Section: Discussionmentioning

confidence: 93%

Identification of genes specific to “oval cells” in the rat 2-acetylaminofluorene/partial hepatectomy model

Batusic

Cimica

Chen

et al. 2005

Histochem Cell Biol

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“…In these situations, liver regeneration is triggered rapidly to restore hepatic function, and hepatic stem cells play an important role in regeneration [1]. Hepatic stem cells in liver tissues have high proliferation potential in vitro and can be induced to differentiate into hepatocytes [2,3]. However, hepatocyte proliferation may be inhibited if the injury is too severe [4], and liver regeneration is often compromised after surgery for malignancies [5,6].…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow-Derived Mesenchymal Stem Cells Promote Hepatic Regeneration after Partial Hepatectomy in Rats

Zhang

et al. 2013

Pathobiology

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Objectives: Our goal was to study the ability of mesenchymal stem cells (MSCs) to stimulate liver regeneration after partial hepatectomy in rats. Methods: MSCs were isolated from bone marrow and cultured in vitro. Their characteristics were analyzed by flow cytometry. After 70% partial hepatectomy, Sprague-Dawley rats were randomly divided into three groups: a control group that was injected with saline, animals that received bone marrow-derived MSCs (BM-MSCs) by tail vein injection (the BM-MSC-TV group) and animals that received BM-MSCs by portal vein injection (the BM-MSC-PV group). The injected BM-MSCs were traced by labeling with 4′,6-diamidino-2-phenylindole, and cell proliferations were determined by immunohistochemical staining with Ki-67 and 5-bromo-2′-deoxyuridine. Results: After the third passage, the cultured BM-MSCs had a fibroblast-like morphology and expressed high levels of stem cell markers CD29 and CD90. The levels of albumin rose significantly in the BM-MSC-TV and BM-MSC-PV groups compared with the control group. The number of 4′,6-diamidino-2-phenylindole-positive liver cells in the BM-MSC-PV group was significantly higher than in the BM-MSC-TV group. The levels of Ki-67 and 5-bromo-2′-deoxyuridine were significantly higher in the BM-MSC-TV and the BM-MSC-PV groups than in the controls. Conclusion: Taken together, these results indicate that BM-MSC injections enhance liver regeneration after partial hepatectomy in rats.

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“…26,27 Many studies have isolated hepatic stem cells or oval cells from liver injury models induced by different chemicals, such as allyl alcohol, 26 carbon tetrachloride, and D-galactosamine. [28][29][30] These models often result in chromosomal abnormalities in hepatic stem cells, which preclude their use in clinical settings. 6 Highquality and phenotypically normal HPCs are very important for cytotherapy (hepatocyte therapy) of liver diseases.…”

Section: Discussionmentioning

confidence: 99%

A Novel Technique for Hepatic Progenitor Cell Isolation From Normal Adult Rat Livers

Guo

et al. 2012

ASAIO Journal

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The transplantation of hepatic progenitor cells (HPCs) is a promising alternate approach to liver transplantation for patients with end-stage liver disease. Here, we report a novel technique for HPCs isolation from normal adult rat livers (no preexposure to chemicals and no injury). HPCs were isolated from normal adult rat livers using a novel four-step collagenase perfusion method followed by density gradient centrifugation. The phenotypic properties of HPCs were characterized by morphological observation, reverse-transcription polymerase chain reaction (RT-PCR), and immunocytochemistry. The results showed that HPCs formed loose colonies and possessed a round or oval shape at culture day 3. These cells proliferated slowly and exhibited progenitor-like characteristics during the 30-day culture period. RT-PCR analysis indicated that the cultured cells were positive for several HPC-specific genes, such as albumin (ALB), alpha-fetoprotein (AFP), cytokeratin 18 (CK18), cytokeratin 19 (CK19), CD45, hepatocyte nuclear factor 1-alpha (HNF-1α), hepatocyte nuclear factor 4-alpha (HNF-4α), and Thy-1. Immunocytochemical staining showed that these cells were consistently positive for ALB, AFP, CK18, CK19, Thy-1, and OV-6. HPCs can be isolated from normal adult rat livers using a simple and effective technique involving four-step collagenase perfusion, further confirming their potential as a strong candidate for hepatocyte therapy.

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Differentiation of putative hepatic stem cells derived from adult rats into mature hepatocytes in the presence of epidermal growth factor and hepatocyte growth factor

Cited by 34 publications

References 22 publications

Identification of genes specific to “oval cells” in the rat 2-acetylaminofluorene/partial hepatectomy model

Identification of genes specific to “oval cells” in the rat 2-acetylaminofluorene/partial hepatectomy model

Bone Marrow-Derived Mesenchymal Stem Cells Promote Hepatic Regeneration after Partial Hepatectomy in Rats

A Novel Technique for Hepatic Progenitor Cell Isolation From Normal Adult Rat Livers

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