Novel hepatic progenitor cell surface markers in the adult rat liver

Yovchev, Mladen I.; Grozdanov, Petar; Joseph, Brigid; Gupta, Sanjeev; Dabeva, Mariana D.

doi:10.1002/hep.21448

Cited by 165 publications

(138 citation statements)

References 42 publications

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“…Moreover, some individual DDR1-expressing oval cells, which are potentially HPCs, were observed near ductular reactions. This novel localization of DDR1 expression in cells that are probably HPCs elucidates the recent detection of DDR1 mRNA in human and rat HPCs 43,44 and deserves further investigation as to whether DDR1 expression has a role in differentiating HPCs into hepatocytes or bile duct cells.…”

Section: Ddr1 In Human Liversupporting

confidence: 64%

Discoidin Domain Receptor 1

Song

Shackel

Wang

et al. 2011

The American Journal of Pathology

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Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell-collagen interactions in chronic liver injury.

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Section: Ddr1 In Human Liversupporting

confidence: 64%

Discoidin Domain Receptor 1

Song

Shackel

Wang

et al. 2011

The American Journal of Pathology

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“…Oval cells are derived from the canal of Hering, and in rodents this canal barely extends beyond the limiting plate ( Figures 4, 5); in contrast, in human liver the organization of the biliary tree is different, with the canal of Hering extending to the proximate third of the lobule [68] and so apparently requiring a name change from oval cells to 'hepatic progenitor cells' (HPCs) [69]. An enormous range of markers has been used to identify ovals cells (Table 2) [70][71][72][73][74][75][76][77][78][79][80][81][82][83] and some, such as Dlk, may signal imminent hepatocyte differentiation [71]. A popular experimental procedure to elicit an oval cell response in rats is to pre-treat the animals with 2-acetylaminofluorene (2-AAF) before performing a two-thirds PH (the 2-AAF/PH protocol).…”

Section: The Facultative Stem Cell Response: Oval/hepatic Progenitor mentioning

confidence: 99%

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Alison

Islam

Lim

2008

The Journal of Pathology

199

149

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The worldwide shortage of donor livers to transplant end stage liver disease patients has prompted the search for alternative cell therapies for intractable liver diseases, such as acute liver failure, cirrhosis and hepatocellular carcinoma (HCC). Under normal circumstances the liver undergoes a low rate of hepatocyte 'wear and tear' renewal, but can mount a brisk regenerative response to the acute loss of two-thirds or more of the parenchymal mass. A body of evidence favours placement of a stem cell niche in the periportal regions, although the identity of such stem cells in rodents and man is far from clear. In animal models of liver disease, adopting strategies to provide a selective advantage for transplanted hepatocytes has proved highly effective in repopulating recipient livers, but the poor success of today's hepatocyte transplants can be attributed to the lack of a clinically applicable procedure to force a similar repopulation of the human liver. The activation of bipotential hepatic progenitor cells (HPCs) is clearly vital for survival in many cases of acute liver failure, and the signals that promote such reactions are being elucidated. Bone marrow cells (BMCs) make, at best, a trivial contribution to hepatocyte replacement after damage, but other BMCs contribute to the hepatic collagen-producing cell population, resulting in fibrotic disease; paradoxically, BMC transplantation may help alleviate established fibrotic disease. HCC may have its origins in either hepatocytes or HPCs, and HCCs, like other solid tumours appear to be sustained by a minority population of cancer stem cells.

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“…Mature hepatocytes, AML-12 cells (ATCC; CRL-2254), immature cholangiocytes, 603B cells (provided by G. Gores, Mayo Clinic, Rochester, MN), 27 and bipotent hepatic epithelial progenitors (ie, oval cells) EpC10 cells (provided by M. Dabeva, Albert Einstein College of Medicine, NY) 28 were grown in regular media then were placed in serum-free media for 18 hours before transforming growth factor (TGF)-β1 (R&D Systems, Minneapolis, MN) at concentration of 2 ng/mL was added. Total RNA and protein were harvested at several different time points during culture (ranging from 0 to 48 hours).…”

Section: Cell Culture Experimentsmentioning

confidence: 99%

“…28 Livers of healthy control mice had only rare PT cells that expressed AE1/AE3 ( Figure 4A). In contrast, increased numbers of periportal ductular cells expressing AE1/AE3 were noted in both HF-control ( Figure 4B) and HF + EtOH ( Figure 4C and D) groups.…”

Section: Expansion Of Liver Progenitor Populations and Ductular Cellsmentioning

confidence: 99%