Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium

Crosby, Heather A.; Kelly, Déirdre; Strain, Alastair J.

doi:10.1053/gast.2001.21175

Cited by 220 publications

(183 citation statements)

References 37 publications

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“…Surprisingly, oval cells/HPCs have attracted little attention in terms of therapeutic potential, perhaps because isolated human cells bearing appropriate markers, eg CD34 or c-kit, only differentiate in vitro into biliary cells [89]. The hepatocyte potential of transplanted oval cells has been clearly demonstrated in animal models: oval cells isolated from LEC rats were transplanted into LEC/Nagase analbuminaemic double mutant rats, where they differentiated into albumin-expressing hepatocytes [90].…”

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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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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“…Classical hematopoietic markers, including Thy-1, c-kit and CD34, are expressed on the surface of oval cells. [22][23][24][25] Additionally, bone marrow transplantation of purified c-kit + , Lin -and Sca-1 + hematopoietic stem cells rescued fumarylacetoacetate (FAH)-deficient mice, an animal model of fatal hereditary tyrosinemia type 1. 26 Crossgender, or cross-strain, bone marrow and whole liver transplants in mice have identified cells in the bone marrow that are capable of repopulating the liver.…”

Section: Oval Cell Originmentioning

confidence: 99%

Oval cell‐mediated liver regeneration: Role of cytokines and growth factors

Lowes

Croager

Olynyk

et al. 2002

J of Gastro and Hepatol

153

123

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In experimental models, which induce liver damage and simultaneously block hepatocyte proliferation, the recruitment of a hepatic progenitor cell population comprised of oval cells is invariably observed. There is a substantial body of evidence to suggest that oval cells are involved in liver regeneration, as they differentiate into hepatocytes and biliary cells. Recently, bone marrow cells were shown to be a source of a stem cells with the capacity to repopulate the liver. Presently, the relationship between bone marrow cells and oval cells is unclear. Investigations will be greatly assisted by the availability of in vitro models based on a knowledge of cytokines that affect oval cells. While the cytokines, which regulate the different hematopoietic lineages, are well characterized, there is relatively little information regarding those that influence oval cells. This review outlines recent developments in the field of oval cell research and focuses on cytokines and growth factors that have been implicated in regulating oval cell proliferation and differentiation.

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“…Independent of their origin, hepatic progenitor cells have been reported to be isolated, propagated and differentiated into hepatic-and pancreatic-islet-like cells in culture [28][29][30][31], thus providing an attractive renewable source of stem cells for cellular therapy. The goal of the current study was to further characterize the potential origin of hepatic progenitor cells in 2-AAF/CCl 4 -treated rat livers and to subsequently isolate and establish a stable oval cell line.…”

Section: Introductionmentioning

confidence: 99%

Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

Corcelle¹,

Stieger

Gjinovci³

et al. 2006

Experimental Cell Research

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Despite extensive studies, the hematopoietic versus hepatic origin of liver progenitor oval cells remains controversial. The aim of this study was to determine the origin of such cells after liver injury and to establish an oval cell line. Rat liver injury was induced by subcutaneous insertion of 2-AAF pellets for 7 days with subsequent injection of CCl 4 . Livers were removed 9 to 13 days post-CCl 4 treatment. Immunohistochemistry was performed using anti-c-kit, OV6, Thy1, CK19, AFP, vWF and Rab3b. Isolated non-parenchymal cells were grown on mouse embryonic fibroblast, and their gene expression profile was characterized by RT-PCR. We identified a subpopulation of OV6/CK19/Rab3b-expressing cells that was activated in the periportal region of traumatized livers. We also characterized a second subpopulation that expressed the HSCs marker c-kit but not Thy1. Although we successfully isolated both cell types, OV6/CK19/Rab3b + cells fail to propagate while c-kit + -HSCs appeared to proliferate for up to 7 weeks. Cells formed clusters which expressed c-kit, Thy1 and albumin. Our results indicate that a bona fide oval progenitor cell population resides within the liver and is distinct from c-kit + -HSCs. Oval cells require the hepatic niche to proliferate, while cells mobilized from the circulation proliferate and transdifferentiate into hepatocytes without evidence of cell fusion.

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Human hepatic stem-like cells isolated using c-kit or CD34 can differentiate into biliary epithelium

Cited by 220 publications

References 37 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

Oval cell‐mediated liver regeneration: Role of cytokines and growth factors

Characterization of two distinct liver progenitor cell subpopulations of hematopoietic and hepatic origins

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