Efficient differentiation of newly derived human embryonic stem cells from discarded blastocysts into hepatocyte‐like cells

Lü, Hong; Wang, Zheng; Zheng, Qing; Li, Jin Hui; Chong, Xiao Qian; Xiao, Shu Dong

doi:10.1111/j.1751-2980.2010.00455.x

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…A typical stem cell cluster‐like structure (Lu et al . )emerged (Fig. , DMSO, white *), of which the cells in the center were very small (Fig.…”

Section: Resultsmentioning

confidence: 99%

Notch is the key factor in the process of fetal liver stem/progenitor cells differentiation into hepatocytes

Wang¹,

You²,

Tao³

et al. 2012

Dev Growth Differ

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Cell transplantation is efficient method to therapy end‐stage liver disease (ESLD). How to punctually induce stem cell differentiation into hepatocyte is still a challenge. Notch plays important roles in embryonic development and cell differentiation. However, during the differentiation process from fetal liver stem/progenitor cells (FLSPCs) to mature hepatocytes, the contribution of Notch, especially which Notch receptor is primarily responsible, is unknown. First, specific Notch receptor responsible for FLSPCs differentiation was identified. On both tissue level and cell level, we found that Notch3 was the only receptor greater expressed in liver tissue at embryonic day (ED) 14 and FLSPCs, compared with the adult liver and BRL cells, respectively. Second, morphological phenotypic and functional aspects were analyzed to evaluate whether Notch inhibition by GSIs (γ‐secretase inhibitors, inhibitor of Notch) promotes the differentiation of FLSPCs into hepatocytes. Results showed that N‐[N‐(3, 5‐Difluorophenacetyl)‐L‐alanyl]‐S‐phenylglycine t‐butyl ester (DAPT) as GSIs was able to induce FLSPCs differentiation into hepatocytes. The differentiated FLSPCs showed similar morphology to mature hepatocytes, expressed hepatic markers indicative of a mature developmental stage, and displayed similar functionality to mature hepatocytes. The differentiation efficiency by GSIs was similar to that by hepatocyte growth factor (HGF) induction. More specifically, as the differentiation of FLSPCs progressed towards hepatocytes, the expression of Notch3 was gradually down‐regulated, consistent with the down‐regulation of other stem cell markers. These findings imply that Notch3 may not only be a regulator of FLSPCs differentiation into hepatocytes, but also be a potential marker of FLSPCs.

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“…A typical stem cell cluster‐like structure (Lu et al . )emerged (Fig. , DMSO, white *), of which the cells in the center were very small (Fig.…”

Section: Resultsmentioning

confidence: 99%

Notch is the key factor in the process of fetal liver stem/progenitor cells differentiation into hepatocytes

Wang¹,

You²,

Tao³

et al. 2012

Dev Growth Differ

View full text Add to dashboard Cite

show abstract

“…Even though feeder‐free cultures using matrigel have been developed, enabling ES cell culture in BAL devices, the risk of introducing murine viruses from matrigel is of concern. There are many reports on the in vitro differentiation of embryonic stem cells to hepatocyte‐like cells . However, none of the available protocols have been delivered at scale and have thereby limit the application of ES‐derived hepatocytes in a BAL .…”

Section: Cell Sources For Liver Tissue Engineeringmentioning

confidence: 99%

Liver tissue engineering and cell sources: issues and challenges

Palakkan

Hay

et al. 2013

Liver International

112

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Liver diseases are of major concern as they now account for millions of deaths annually. As a result of the increased incidence of liver disease, many patients die on the transplant waiting list, before a donor organ becomes available. To meet the huge demand for donor liver, alternative approaches using liver tissue engineering principles are being actively pursued. Even though adult hepatocytes, the primary cells of the liver are most preferred for tissue engineering of liver, their limited availability, isolation from diseased organs, lack of in vitro propagation and deterioration of function acts as a major drawback to their use. Various approaches have been taken to prevent the functional deterioration of hepatocytes including the provision of an adequate extracellular matrix and co-culture with non-parenchymal cells of liver. Great progress has also been made to differentiate human stem cells to hepatocytes and to use them for liver tissue engineering applications. This review provides an overview of recent challenges, issues and cell sources with regard to liver tissue engineering.

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“…Following the HD culture, hEBs may undergo suspension culture for further compaction before being used in a differentiation protocol. A few studies have shown differentiation of HD-produced human EBs to several cell types, including hematopoietic cells [52], cardiomyocytes [53], and hepatocytes [54]. These investigations indicate propensities of the HD-produced EBs to progress toward cell types of all three germ layers.…”

Section: Figmentioning

confidence: 99%

Engineering Strategies for the Formation of Embryoid Bodies from Human Pluripotent Stem Cells

Pettinato

Wen

Zhang

2015

Stem Cells and Development

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Human pluripotent stem cells (hPSCs) are powerful tools for regenerative therapy and studying human developmental biology, attributing to their ability to differentiate into many functional cell types in the body. The main challenge in realizing hPSC potential is to guide their differentiation in a well-controlled manner. One way to control the cell differentiation process is to recapitulate during in vitro culture the key events in embryogenesis to obtain the three developmental germ layers from which all cell types arise. To achieve this goal, many techniques have been tested to obtain a cellular cluster, an embryoid body (EB), from both mouse and hPSCs. Generation of EBs that are homogeneous in size and shape would allow directed hPSC differentiation into desired cell types in a more synchronous manner and define the roles of cell-cell interaction and spatial organization in lineage specification in a setting similar to in vivo embryonic development. However, previous success in uniform EB formation from mouse PSCs cannot be extrapolated to hPSCs possibly due to the destabilization of adherens junctions on cell surfaces during the dissociation into single cells, making hPSCs extremely vulnerable to cell death. Recently, new advances have emerged to form uniform human embryoid bodies (hEBs) from dissociated single cells of hPSCs. In this review, the existing methods for hEB production from hPSCs and the results on the downstream differentiation of the hEBs are described with emphases on the efficiency, homogeneity, scalability, and reproducibility of the hEB formation process and the yield in terminal differentiation. New trends in hEB production and directed differentiation are discussed.

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Efficient differentiation of newly derived human embryonic stem cells from discarded blastocysts into hepatocyte‐like cells

Abstract: Three hES cell lines have been successfully isolated and cultured from discarded human blastocysts. The hES cells can be efficiently differentiated into hepatocyte-like cells using the EB system. These cells possess the potential for treatment of liver diseases.

Cited by 8 publications

References 11 publications

Notch is the key factor in the process of fetal liver stem/progenitor cells differentiation into hepatocytes

Notch is the key factor in the process of fetal liver stem/progenitor cells differentiation into hepatocytes

Liver tissue engineering and cell sources: issues and challenges

Engineering Strategies for the Formation of Embryoid Bodies from Human Pluripotent Stem Cells

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