Role of cholangioles in restoration of the liver of the mouse after dietary injury

Wilson, Jesse W.; Leduc, Elizabeth H.

doi:10.1002/path.1700760213

Cited by 159 publications

(69 citation statements)

References 6 publications

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“…2 These hHpSCs are recognizable in these histological and immunohistochemical studies on sections of livers from varying age donors complementing the prior findings using flow cytometric and molecular analyses of hHpSCs versus hHBs isolated from fetal versus adult livers. 2,3 The hHpSCs of the postnatal liver have been hypothesized to exist in the canals of Hering and the smallest ductules located periportally 14,30 and are shown now to contain label-retaining cells, properties known for stem cell populations. 9 It has been assumed that hHpSCs are not involved in normal maintenance of liver parenchyma or in repair after mild injury or after partial hepatectomy.…”

Section: Discussionmentioning

confidence: 99%

The stem cell niche of human livers: Symmetry between development and regeneration

et al. 2008

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Section: Discussionmentioning

confidence: 99%

The stem cell niche of human livers: Symmetry between development and regeneration

et al. 2008

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“…HOC have long been speculated to be involved in the process of hepatocarcinogenesis. 48 It would be interesting to know whether or not hepatocellular carcinomas also express high levels of Thy-1. If they express the Thy-1 antigen as the neuronal tumors do, it may be tempting to speculate that Thy-1 may actually have an important role HEPATOLOGY Vol.…”

Section: Discussionmentioning

confidence: 99%

Hepatic oval cells express the hematopoietic stem cell marker thy-1 in the rat

et al. 1998

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Hepatic oval cells (HOC) are a small subpopulation of cells found in the liver when hepatocyte proliferation is inhibited and followed by some type of hepatic injury. HOC can be induced to proliferate using a 2-acetylaminofluorene (2-AAF)/hepatic injury (i.e., CCl 4 , partial hepatectomy [PHx]) protocol. These cells are believed to be bipotential, i.e., able to differentiate into hepatocytes or bile ductular cells. In the past, isolation of highly enriched populations of these cells has been difficult. Thy-1 is a cell surface marker used in conjunction with CD34 and lineage-specific markers to identify hematopoietic stem cells. Thy-1 antigen is not normally expressed in adult liver, but is expressed in fetal liver, presumably on the hematopoietic cells. We report herein that HOC express high levels of Thy-1. Immunohistochemistry revealed that the cells expressing Thy-1 were indeed oval cells, because they also expressed ␣-fetoprotein (AFP), ␥-glutamyl transpeptidase (GGT), cytokeratin 19 (CK-19), OC.2, and OV-6, all known markers for oval cell identification. In addition, the Thy-1 ؉ cells were negative for desmin, a marker specific for Ito cells. Using Thy-1 antibody as a new marker for the identification of oval cells, a highly enriched population was obtained. Using flow cytometric methods, we isolated a 95% to 97% pure Thy-1 ؉ oval cell population. Our results indicate that cell sorting using Thy-1 could be an attractive tool for future studies, which would facilitate both in vivo and in vitro studies of HOC. (HEPATOLOGY 1998;27:433-445.) Adequate data have been gathered that show that oval cells exist in the treated liver, but their place of origin and their role in liver development, regeneration, and carcinogenesis remains enigmatic. Oval cells increase in numbers when hepatocyte proliferation is suppressed. 2-Acetylaminofluorene (2-AAF) given before and during hepatic injury by a partial hepatectomy of two thirds (PHx) results in suppression of proliferation of hepatocytes and expansion of a population of oval cells.

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“…Early observations of cell proliferation in response to chemical hepatocarcinogenesis led to the suggestion that such a population existed, [1][2][3] and since then a large body of experimental evidence has supported this concept. [4][5][6][7][8] An alternative view is that the small oval cells proliferating in these models represent proliferating ductular cells.…”

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confidence: 99%

“…14 The morphology and phenotypes of the putative stem cells generally reflect such an origin: they are morphologically and phenotypically like small cholangiocytes, albeit with varying degrees of hepatocytic features depending on the models examined. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] However, in experimental work by Yavorkovsky et al, 15 periportal necrosis of allyl alcohol toxicity resulted in a ''null cell'' proliferation that was negative not only for hepatocyte markers, but also for cholangiocyte markers. This could be explained in two ways: first, either the null cells derive from the canals of Hering and/or biliary tree, and lose cholangiocyte marker expression in the earliest stages of proliferation only to regain them after a short while or, second, that the cholangiocytes lining the most peripheral branches of the biliary tree are not the only source for these cells.…”

mentioning

confidence: 99%

Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation

et al. 2000

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Following a report of skeletal muscle regeneration from bone marrow cells, we investigated whether hepatocytes could also derive in vivo from bone marrow cells. A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants from age-matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2, 4, and 6 posttransplantation (n ‫؍‬ 3 for each time point).

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Role of cholangioles in restoration of the liver of the mouse after dietary injury

Cited by 159 publications

References 6 publications

The stem cell niche of human livers: Symmetry between development and regeneration

The stem cell niche of human livers: Symmetry between development and regeneration

Hepatic oval cells express the hematopoietic stem cell marker thy-1 in the rat

Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation

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