Evidence map›Paper›PMID 24020366›Full record

ArticleStem cells and development2014

Spheroid culture for enhanced differentiation of human embryonic stem cells to hepatocyte-like cells.

Kartik Subramanian, Derek Jason Owens, Ravali Raju, Meri Firpo, Timothy D O'Brien, Catherine M Verfaillie, Wei-Shou Hu

Abstract read
In one paragraph

Article in Stem cells and development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

  1. Article
  2. Review
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  5. Review
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  7. Review
  8. Generation of Hepatocyte Organoids from Human iPS Cells.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  9. Review
  10. Article
  11. Stem cell-derived polarized hepatocytes.Nature communications · 2020
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Kartik Subramanian1 Department of Chemical Engineering and Materials Science, University of Minnesota , Minneapolis, Minnesota.
Derek Jason Owens
Ravali Raju
Meri Firpo
Timothy D O'Brien
Catherine M Verfaillie
Wei-Shou Hu

Funding

NIGMS NIH HHS GM08347
6 · The paper itself

Abstract

Stem cell-derived hepatocyte-like cells hold great potential for the treatment of liver disease and for drug toxicity screening. The success of these applications hinges on the generation of differentiated cells with high liver specific activities. Many protocols have been developed to guide human embryonic stem cells (hESCs) to differentiate to the hepatic lineage. Here we report cultivation of hESCs as three-dimensional aggregates that enhances their differentiation to hepatocyte-like cells. Differentiation was first carried out in monolayer culture for 20 days. Subsequently cells were allowed to self-aggregate into spheroids. Significantly higher expression of liver-specific transcripts and proteins, including Albumin, phosphoenolpyruvate carboxykinase, and asialoglycoprotein receptor 1 was observed. The differentiated phenotype was sustained for more than 2 weeks in the three-dimensional spheroid culture system, significantly longer than in monolayer culture. Cells in spheroids exhibit morphological and ultrastructural characteristics of primary hepatocytes by scanning and transmission electron microscopy in addition to mature functions, such as biliary excretion of metabolic products and cytochrome P450 activities. This three-dimensional spheroid culture system may be appropriate for generating high quality, functional hepatocyte-like cells from ESCs.

Indexed as

AlbuminsAryl Hydrocarbon HydroxylasesAsialoglycoprotein ReceptorCell DifferentiationCells, CulturedCytochrome P-450 CYP1A1Cytochrome P-450 CYP1A2Cytochrome P-450 CYP2B6Cytochrome P-450 Enzyme SystemCytochrome P450 Family 2Embryonic Stem CellsHepatocytesHumansLiverOxazinesPhosphoenolpyruvate Carboxykinase (ATP)AlbuminsAryl Hydrocarbon HydroxylasesASGR1 protein, humanAsialoglycoprotein ReceptorCYP1A1 protein, humanCYP1A2 protein, humanCYP2B6 protein, humanCYP2B7P protein, humanCytochrome P-450 CYP1A1Cytochrome P-450 CYP1A2Cytochrome P-450 CYP2B6Cytochrome P-450 Enzyme SystemCytochrome P450 Family 2OxazinesPhosphoenolpyruvate Carboxykinase (ATP)resorufin

Identifiers

PMID24020366
PMCPMC3887452

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.