Differentiation and isolation of hepatic-like cells from human embryonic stem cells

Lavon, Neta; Yanuka, Ofra; Benvenisty, Nissim

doi:10.1111/j.1432-0436.2004.07205002.x

Cited by 233 publications

(149 citation statements)

References 28 publications

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“…that ES cells can be differentiated into hepatocyte-like cells [1][2][3][4][5][6] . ES cell-derived hepatocytes would be useful as a source of material for cell transplantation, bioartificial liver (BAL) support devices, studies on hepatocyte biology and hepatitis viruses and for drug testing.…”

Section: Protocols Have Been Developed To Differentiate and Enrich Vamentioning

confidence: 99%

“…Spontaneous differentiation of ES cells can be accomplished in serum-containing medium through the formation of embryoid bodies (EB)-containing cells representing ectoderm, mesoderm and endoderm lineages. Subsequent inoculation of the EB-derived cells on adherent matrix substrates allows spontaneous differentiation, producing occasional hepatocyte-like cells 3,6 . In vivo differentiation of mouse ES cells has also been accomplished by transplantation into the livers of carbon tetrachloride-treated mice.…”

Section: Protocols Have Been Developed To Differentiate and Enrich Vamentioning

confidence: 99%

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Differentiation of mouse embryonic stem cells to hepatocyte-like cells by co-culture with human liver nonparenchymal cell lines

et al. 2007

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This protocol describes a co-culture system for the in vitro differentiation of mouse embryonic stem cells into hepatocyte-like cells. Differentiation involves four steps: (i) formation of embryoid bodies (EB), (ii) induction of definitive endoderm from 2-d-old EBs, (iii) induction of hepatic progenitor cells and (iv) maturation into hepatocyte-like cells. Differentiation is completed by 16 d of culture. EBs are formed, and cells can be induced to differentiate into definitive endoderm by culture in Activin A and fibroblast growth factor 2 (FGF-2). Hepatic differentiation and maturation of cells is accomplished by withdrawal of Activin A and FGF-2 and by exposure to liver nonparenchymal cell-derived growth factors, a deleted variant of hepatocyte growth factor (dHGF) and dexamethasone. Approximately 70% of differentiated embryonic stem (ES) cells express albumin and can be recovered by albumin promoter-based cell sorting. The sorted cells produce albumin in culture and metabolize ammonia, lidocaine and diazepam at approximately two-thirds the rate of primary mouse hepatocytes.

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Section: Protocols Have Been Developed To Differentiate and Enrich Vamentioning

confidence: 99%

Section: Protocols Have Been Developed To Differentiate and Enrich Vamentioning

confidence: 99%

Differentiation of mouse embryonic stem cells to hepatocyte-like cells by co-culture with human liver nonparenchymal cell lines

et al. 2007

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“…Protooncogenes became active in the area [122], collecting stem cells to the wound [73], which are repaired by their differentiation [123]. After the process, all of the activation genes are down-regulated, or tumor suppressors are activated [124], and the normal homeostasis became re-established. In the cancerous state, the repair conditions are not blocked after finishing the reparation process itself.…”

Section: Generalisationmentioning

confidence: 99%

Connections between Warburg’s and Szentgyorgyi’s Approach about the Causes of Cancer

Gp¹,

Szász²,

Hegyi³

2016

J Neoplasm

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Numerous theories and hypotheses are published about the causes of cancer and its hallmarks. Two remarkable principles were established and debated for a long time. The first is the Warburg-effect, which based on mitochondrial dysfunction, connected to the intensive metabolic activity of the malignancy. The other is the Szentgyorgyi's effect which describes the malignancy by changing of the cellular state (α ↔ β) explained by evolutional biology and supported by definitely improved dielectric properties of the malignant tissue from their normal counterpart while these theories have stable explanations, developed many controversies. Both are partial of completely revised time-by-time, showing new insights with new evidence as additions to these old ideas. Our objective is to demonstrate connections between these theories and start new considerations in the actual debates.

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“…This first clue of endodermal differentiation led us to analyze the potential of human ES cells to differentiate into hepatic cells and the spontaneous differentiation of human ES cells into hepatic-like cells was demonstrated [Lavon et al, 2004]. Human hepatic-like cells were isolated and characterized for their phenotype.…”

Section: Embryonic Stem Cells and Hepatocytesmentioning

confidence: 99%

Study of hepatocyte differentiation using embryonic stem cells

Lavon

Benvenisty

2005

J of Cellular Biochemistry

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115

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The liver has many crucial functions including metabolizing dietary molecules, detoxifying compounds, and storing glycogen. The hepatocytes, comprising most of the liver organ, progressively modify their gene expression profile during the fetal development according to their roles in the different phases of development. Embryonic stem (ES) cells serve as a major tool in understanding liver development. These cells may also serve as a source of hepatic cells for cellular therapy. In this review, we aim to summarize the research that has been performed in the field of hepatocyte differentiation from mouse and human ES cells. We discuss the various methodologies for the differentiation of ES cells towards hepatic cells using either spontaneous or directed differentiation protocols. Although many protocols for differentiating ES cells to hepatic cells have been developed, the analysis of their status is not trivial and can lead to various conclusions. Hence, we discuss the issues of analyzing hepatocytes by means of the specificity of the markers for hepatocytes and the status of the cells as fetal or adult hepatocytes.

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Differentiation and isolation of hepatic-like cells from human embryonic stem cells

Cited by 233 publications

References 28 publications

Differentiation of mouse embryonic stem cells to hepatocyte-like cells by co-culture with human liver nonparenchymal cell lines

Differentiation of mouse embryonic stem cells to hepatocyte-like cells by co-culture with human liver nonparenchymal cell lines

Connections between Warburg’s and Szentgyorgyi’s Approach about the Causes of Cancer

Study of hepatocyte differentiation using embryonic stem cells

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