Comparison of liver progenitor cells in human atypical ductular reactions with those seen in experimental models of liver injury

Sell, Stewart

doi:10.1002/hep.510270202

Cited by 130 publications

(122 citation statements)

References 109 publications

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“…Human hepatocytes had a normal canalicular and sinusoidal pole and showed no abnormalities, besides the glycogen accumulation. Hepatic progenitor cells of types I (most undifferentiated type) and III (having some hepatic features) 13,14 were present in the chimeric liver. Some progenitor cells showed signs of damage, indicating a mouse origin, and were forming a chimeric canalicular structure with a human hepatocyte (Fig.…”

Section: Histological Studies Of Uninfected Chimeric Liversmentioning

confidence: 99%

Morphological and biochemical characterization of a human liver in a uPA‐SCID mouse chimera†‡

et al. 2005

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D espite decades of research, the processes that govern liver development and regeneration are only partially understood. A good understanding of the mechanisms that play a role in these processes is important because it may lead to new treatments of human liver diseases. Several in vivo experimental conditions have been used to study liver regeneration and repair and the interaction of different cell types in these processes. These include partial hepatectomy, administration of toxic compounds, or a combination of both, and transgenic expression of certain proteins. 1,2 In contrast to in vitro experiments, these approaches raise fewer questions concerning the influence of artificial matrices on the function and behavior of hepatocytes and other liver cell types.Although these procedures have generated useful information on rodent liver regeneration, stem cell activation, and other processes, extrapolating these findings to the Abbreviations: uPA, urokinase plasminogen activator; HBV, hepatitis B virus; HCV, hepatitis C virus; HBsAg, hepatitis B surface antigen; HBeAg, hepatitis B e antigen; PAS, periodic-acid-Schiff. From the

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Section: Histological Studies Of Uninfected Chimeric Liversmentioning

confidence: 99%

Morphological and biochemical characterization of a human liver in a uPA‐SCID mouse chimera†‡

et al. 2005

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“…Oval cells are not the only progenitor populations present in adult liver. Four classes of hepatic stem-like cells have been defined in human liver (Sell 1998), one or more of which may correspond to stemlike cells described in normal and injured rat liver (Novikoff et al 1996;Tateno and Yoshizato 1996;Hixson and Fowler 1997;Gordon et al 2000;Hixson et al 2000). These findings led to the conclusion that the liver is populated with bipotent progenitor cells in various states of differentiation or maturation (Sell 1998).…”

Section: Introductionmentioning

confidence: 97%

Monoclonal antibody to novel cell surface epitope on Hsc70 promotes morphogenesis of bile ducts in newborn rat liver

Mills

Haskell

Callanan

et al. 2010

Cell Stress and Chaperones

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“…6 In experimental animal models reproducing liver injuries, inhibition of hepatocyte proliferation contributes to activate this hepatic progenitor cell compartment, 7 which is also found to favor hepatocarcinoma development. 8 Indeed, pools of small epithelial cells characterized by stem and fetal markers, and immature biliary and hepatocytic cells expressing specific functional markers have been described in tumors. 8 The origin of hepatic progenitors during carcinogenesis is still extensively debated.…”

mentioning

confidence: 99%

“…8 Indeed, pools of small epithelial cells characterized by stem and fetal markers, and immature biliary and hepatocytic cells expressing specific functional markers have been described in tumors. 8 The origin of hepatic progenitors during carcinogenesis is still extensively debated. It can occur from aberrant proliferation and differentiation of hepatic progenitors or from their immediate progeny.…”

mentioning

confidence: 99%

Transdifferentiation of hepatocyte‐like cells from the human hepatoma HepaRG cell line through bipotent progenitor†

et al. 2007

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Hepatic tumors, exhibiting mature hepatocytes and undifferentiated cells merging with cholangiocyte and hepatocyte phenotypes, are frequently described. The mechanisms by which they occur remain unclear. We report differentiation and transdifferentiation behaviors of human HepaRG cells isolated from a differentiated tumor developed consecutively to chronic HCV infection. We demonstrate that, in vitro, proliferating HepaRG cells differentiate toward hepatocyte-like and biliary-like cells at confluence. If hepatocyte-like cells are selectively isolated and cultured at high cell density, they proliferate and preserve their differentiation status. However, when plated at low density, they transdifferentiate into hepatocytic and biliary lineages through a bipotent progenitor. In accordance, transplantation of either undifferentiated or differentiated HepaRG cells in uPA/SCID mouse damaged liver gives rise mainly to functional human hepatocytes infiltrating mouse parenchyma. Analysis of the differentiation/transdifferentiation process reveals that: (1) H epatic tumors with combined hepatocellular cholangiocarcinoma have been frequently described for instance, hepatoblastoma with cholangioblastic features in young patients 1 and HCCs with dual expression of hepatocyte and bile duct markers in adult patients suffering from diseases related to HCV and/or HBV infection. 2 Such tumors usually contain mature hepatocytes and so-called transitional areas that consist of undifferentiated cells that have morphological and immunological features of both hepatocytes and cholangiocytes. 3 Co-expression of hepatocytic and biliary markers suggests involvement of hepatic progenitor cells in development of these human tumors and supports the concept of genetic events to explain their abnormal growth during tumor formation. 4 However, mechanisms of occurrence of these progenitors and abnormal control of their expansion and differentiation are still unclear.Hepatic progenitor cells, also referred to as oval cells in rodents, have been defined as immature epithelial cells able to differentiate toward both biliary and hepatocytic lineages. The smallest ramification of the biliary tree in adult liver, the canal of Hering, may constitute the niche for these hepatic progenitor cells. 5 They are few in number, and because bile ductular and hepatocytic cells have a tremendous capacity to proliferate and differentiate, heAbbreviations: BrdU, bromodeoxyuridine; HNF, hepatocyte nuclear factor; RT, reverse transcription.

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Comparison of liver progenitor cells in human atypical ductular reactions with those seen in experimental models of liver injury

Cited by 130 publications

References 109 publications

Morphological and biochemical characterization of a human liver in a uPA‐SCID mouse chimera†‡

Morphological and biochemical characterization of a human liver in a uPA‐SCID mouse chimera†‡

Monoclonal antibody to novel cell surface epitope on Hsc70 promotes morphogenesis of bile ducts in newborn rat liver

Transdifferentiation of hepatocyte‐like cells from the human hepatoma HepaRG cell line through bipotent progenitor†

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