Hepatocyte differentiation from embryonic stem cells and umbilical cord blood cells

Teramoto, Koji; Asahina, Kinji; Kumashiro, Yuji; Kakinuma, Sei; Chinzei, Ryoko; Shimizu-Saito, Keiko; Tanaka, Yujiro; Teraoka, Hirobumi; Arii, Shigeki

doi:10.1007/s00534-005-0980-5

Cited by 35 publications

(19 citation statements)

References 76 publications

(178 reference statements)

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“…The differentiation rate in their protocol was about 50%, and the hepatocytes obtained [49] demonstrated that human cord matrix stem cells cultured with growth factors show hepatocyte characteristics like cytochrome P450-34A expression, glycogen storage and urea production. In addition, when transplanted into hepatectomized immune-deficient mice, small clusters of human cells expressing albumin and alpha-fetoprotein appear, thereby demonstrating the good engraftment and differentiation capacity of the transplanted cells [50,51] . Placenta is another potential source of stem cells.…”

Section: Fetal Annex Stem Cellsmentioning

confidence: 99%

Stem cells for end stage liver disease: How far have we got?

Lorenzini¹,

Gitto²,

Grandini³

et al. 2008

WJG

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End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.

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Section: Fetal Annex Stem Cellsmentioning

confidence: 99%

Stem cells for end stage liver disease: How far have we got?

Lorenzini¹,

Gitto²,

Grandini³

et al. 2008

WJG

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“…Presently remarkable progress has been made in understanding the differentiation of ES cells into neural [Hancock et al, 2000], hematopoietic [Baron, 2001;Perlingeiro et al, 2001;Feng et al, 2005], endothelial , vascular [Sone et al, 2003;Yurugi-Kobayashi et al, 2003;Suzuki et al, 2005], and pancreatic stem/progenitor cells and then various mature cells. However, limited knowledge has been acquired for the differentiation of hepatic progenitor/stem cells, although hepatic differentiation from murine and human ES cells both in vitro and in vivo has been reported in recent studies [Hamazaki et al, 2001;Chinzei et al, 2002;Choi et al, 2002;Ishizaka et al, 2002;Jones et al, 2002;Miyashita et al, 2002;Yamada et al, 2002;Yin et al, 2002;Yamamoto et al, 2003;Kania et al, 2004;Ogawa et al, 2005;Teramoto et al, 2005;Teratani et al, 2005]. These hepatic cells from ES cells expressed some typical markers of mature hepatocytes and showed sufficient functions to rescue experimental liver injury when transplanted in vivo, which raised the hope to generate a transplantable cell source for the treatment of end-stage liver diseases.…”

mentioning

confidence: 99%

In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate

Zhou

Xiang

Shao

et al. 2006

J of Cellular Biochemistry

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Recently it was shown that embryonic stem (ES) cells could differentiate into hepatocytes both in vitro and in vivo, however, prospective hepatic progenitor cells have not yet been isolated and characterized from ES cells. Here we presented a novel 4-step procedure for the differentiation of mouse ES cells into hepatic progenitor cells and then hepatocytes. The differentiated hepatocytes were identified by morphological, biochemical, and functional analyses. The hepatic progenitor cells were isolated from the cultures after the withdrawal of sodium butyrate, which was characterized by scant cytoplasm, ovoid nuclei, the ability of rapid proliferation, expression of a series of hepatic progenitor cell markers, and the potential of differentiation into hepatocytes and bile duct-like cells under the proper conditions that favor hepatocyte and bile epithelial differentiation. The differentiation of hepatocytes from hepatic progenitor cells was characterized by a number of hepatic cell markers including albumin secretion, upregulated transcription of glucose-6-phophatase and tyrosine aminotransferase, and functional phenotypes such as glycogen storage. The results from our experiments demonstrated that ES cells could differentiate into a novel bipotential hepatic progenitor cell and mature into hepatocytes with typical morphological, phenotypic and functional characteristics, which provides an useful model for the studies of key events during early liver development and a potential source of transplantable cells for cell-replacement therapies.

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“…Mouse ESCs have also been shown to differentiate into mature hepatocytes by growth factors (Hamazaki et al, 2001;Jones et al, 2002). In addition, mouse ESC-derived hepatocytes have been transplanted into animal models of liver injury, resulting in improved liver function Teramoto et al, 2005;Yamamoto et al, 2003). Research investigating hepatic differentiation from hESCs has been limited (Lavon et al, 2004;Rambhatla et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro

Baharvand

Hashemi²,

Ashtiani³

et al. 2006

Int. J. Dev. Biol.

384

267

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Human embryonic stem cells (hESCs) have enormous potential as a source of cells for cell replacement therapies and as a model for early human development. In this study we examined the differentiating potential of hESCs into hepatocytes in two-and three-dimensional (2D and 3D) culture systems. Embryoid bodies (EBs) were inserted into a collagen scaffold 3D culture system or cultured on collagen-coated dishes and stimulated with exogenous growth factors to induce hepatic histogenesis. Immunofluorescence analysis revealed the expression of albumin (ALB) and cytokeratin-18 (CK-18). The differentiated cells in 2D and 3D culture system displayed several characteristics of hepatocytes, including expression of transthyretin, α-1-antitrypsin, cytokeratin 8, 18, 19, tryptophan-2,3-dioxygenase, tyrosine aminotransferase, glucose-6-phosphatase (G6P), cytochrome P450 subunits 7a1 and secretion of alpha-fetoprotein (AFP) and ALB and production of urea. In 3D culture, ALB and G6P were detected earlier and higher levels of urea and AFP were produced, when compared with 2D culture. Electron microscopy of differentiated hESCs showed hepatocyte-like ultrastructure, including glycogon granules, welldeveloped Golgi apparatuses, rough and smooth endoplasmic reticuli and intercellular canaliculi. The differentiation of hESCs into hepatocyte-like cells within 3D collagen scaffolds containing exogenous growth factors, gives rise to cells displaying morphological features, gene expression patterns and metabolic activities characteristic of hepatocytes and may provide a source of differentiated cells for treatment of liver diseases.

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Hepatocyte differentiation from embryonic stem cells and umbilical cord blood cells

Cited by 35 publications

References 76 publications

Stem cells for end stage liver disease: How far have we got?

Stem cells for end stage liver disease: How far have we got?

In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate

Differentiation of human embryonic stem cells into hepatocytes in 2D and 3D culture systems in vitro

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