Enrichment of a bipotent hepatic progenitor cell from naïve adult liver tissue

Wright, Natasha R.; Samuelson, Lisa; Walkup, Maggie H.; Chandrasekaran, Prakash; Gerber, David A.

doi:10.1016/j.bbrc.2007.11.129

Cited by 27 publications

(23 citation statements)

References 31 publications

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“…By labelling cells with BrdU after a necrogenic dose of acetaminophen, and then administering another dose 2 weeks later to induce several divisions of previously labelled cells, so-called label-retaining cells (LRCs), considered to be slowly dividing stem cells, were found as both cholangiocytes of interlobular ducts and peribiliary hepatocytes and so-called null cells [26]. It is not clear if the latter cells correspond to the peribiliary Sca-1 + cells, also found in the murine liver [27]. In human liver as well, rare putative stem cells that strongly express STAT3 and the embryonic stem cell-associated pluripotency-associated factors Oct4 and nanog are apparently also located near portal tracts [28].…”

Section: Hepatocytesmentioning

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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Section: Hepatocytesmentioning

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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“…Most importantly, upon transplantation into a CCl 4 -treated mice, these isolated liver epithelial progenitor cells migrated into the liver parenchyma and differentiated into hepatocytes [4]. Furthermore, several groups [5][6][7] have asserted that bipotent HPCs reside in the liver tissues of uninjured adult mice. In addition, endodermal cell populations isolated from liver tissues of a transgenic mouse were capable of differentiating into both hepatic and biliary cell lineages; Fujikawa et al [8] believes that these cells are HPCs.…”

Section: Introductionmentioning

confidence: 96%

Identification and location of label retaining cells in mouse liver

Lu³

2009

J Gastroenterol

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“…However, when hepatocyte replication is blocked, liver progenitor cells, called oval cells in rodents, are able to proliferate and differentiate into mature hepatocytes [1]. A number of different liver progenitor cell populations derived from adult liver have been reported [2][3][4][5][6][7][8][9][10]. Oval cells are considered to be transit amplifying cells and are reported to differentiate into both the hepatocytic and cholangiocytic lineages in vitro [11].…”

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confidence: 99%

CD24-Positive Cells from Normal Adult Mouse Liver Are Hepatocyte Progenitor Cells

Qiu

Hernández

Dean

et al. 2011

Stem Cells and Development

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The identification of specific cell surface markers that can be used to isolate liver progenitor cells will greatly facilitate experimentation to determine the role of these cells in liver regeneration and their potential for therapeutic transplantation. Previously, the cell surface marker, CD24, was observed to be expressed on undifferentiated bipotential mouse embryonic liver stem cells and 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced oval cells. Here, we describe the isolation and characterization of a rare, primary, nonhematopoietic, CD24 + progenitor cell population from normal, untreated mouse liver. By immunohistochemistry, CD24-expressing cells in normal adult mouse liver were colocalized with CK19-positive cholangiocytes. This nonhematopoietic (CD45 -, Ter119 -) CD24 + cell population isolated by flow cytometry represented 0.04% of liver cells and expressed several markers of liver progenitor/oval cells. The immunophenotype of nonhematopoietic CD24 + cells was CD133, Dlk, and Sca-1 high, but c-Kit, Thy-1, and CD34 low. The CD24 + cells had increased expression of CK19, epithelial cell adhesion molecule, Sox 9, and FN14 compared with the unsorted cells. Upon transplantation of nonhematopoietic CD24 + cells under the sub-capsule of the livers of Fah knockout mice, cells differentiated into mature functional hepatocytes. Analysis of X and Y chromosome complements were used to determine whether or not fusion of the engrafted cells with the recipient hepatocytes occurred. No cells were found that contained XXXY or any other combination of donor and host sex chromosomes as would be expected if cell fusion had occurred. These results suggested that CD24 can be used as a cell surface marker for isolation of hepatocyte progenitor cells from normal adult liver that are able to differentiate into hepatocytes.

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Enrichment of a bipotent hepatic progenitor cell from naïve adult liver tissue

Cited by 27 publications

References 31 publications

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

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

Identification and location of label retaining cells in mouse liver

CD24-Positive Cells from Normal Adult Mouse Liver Are Hepatocyte Progenitor Cells

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