Evidence map›Paper›PMID 29379855›Full record

ArticleCellular and molecular gastroenterology and hepatology2018

A Cell Culture Platform to Maintain Long-term Phenotype of Primary Human Hepatocytes and Endothelial Cells.

Brenton R Ware, Mitchell J Durham, Chase P Monckton, Salman R Khetani

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
4.8field-weighted citation impact, top 4% of its field
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

54 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
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  5. In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025
    Review
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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

4 authors at 2 institutions in 1 country.

Brenton R WareSchool of Biomedical Engineering, Colorado State University, Fort Collins, Colorado.
Mitchell J DurhamSchool of Biomedical Engineering, Colorado State University, Fort Collins, Colorado.
Chase P MoncktonDepartment of Bioengineering, University of Illinois at Chicago, Chicago, Illinois.
Salman R KhetaniSchool of Biomedical Engineering, Colorado State University, Fort Collins, Colorado.
University of Illinois Chicago · USColorado State University · US

Funding

Functionally maturing iPSC-derived human hepatocytes in 3D microgelsR21ES027622 · NIEHS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KHETANI, SALMAN R · 2017 to 2018
$427k
NIEHS NIH HHS R21 ES027622
6 · The paper itself

Abstract

BACKGROUND AND

aimsModeling interactions between primary human hepatocytes (PHHs) and primary human liver sinusoidal endothelial cells (LSECs)

methodsPrimary human LSECs or human umbilical vein endothelial cells as the nonliver control were cocultivated with micropatterned PHH colonies (to control homotypic interactions) followed by an assessment of PHH morphology and functions (albumin and urea secretion, and cytochrome P-450 2A6 and 3A4 enzyme activities) over 3 weeks. Endothelial phenotype was assessed via gene expression patterns and scanning electron microscopy to visualize fenestrations. Hepatic responses in PHH/endothelial cocultures were benchmarked against responses in previously developed PHH/3T3-J2 fibroblast cocultures. Finally, PHH/fibroblast/endothelial cell tricultures were created and characterized as described previously.

resultsLSECs, but not human umbilical vein endothelial cells, induced PHH albumin secretion for ∼11 days; however, neither endothelial cell type could maintain PHH morphology and functions to the same magnitude/longevity as the fibroblasts. In contrast, both PHHs and endothelial cells displayed stable phenotype for 3 weeks in PHH/fibroblast/endothelial cell tricultures; furthermore, layered tricultures in which PHHs and endothelial cells were separated by a protein gel to mimic the space of Disse displayed similar functional levels as the coplanar tricultures.

conclusionsPHH/fibroblast/endothelial tricultures constitute a robust platform to elucidate reciprocal interactions between PHHs and endothelial cells in physiology, disease, and after drug exposure.

Indexed as

3T3-J2 FibroblastsCD31, cluster of differentiation 31CD54, cluster of differentiation 54cDNA, complementary DNACYP450, cytochrome P-450ECM, extracellular matrixF8, factor VIIIGAPDH, glyceraldehyde 3-phosphate dehydrogenaseHUVECsHUVECs, human umbilical vein endothelial cellsLSECsLSECs, liver sinusoidal endothelial cellsMicropatterned CoculturesNPCs, nonparenchymal cellsPHHs, primary human hepatocytesSEM, scanning electron microscopeTriculturesvWF, von Willebrand factor

Identifiers

PMID29379855
PMCPMC5782488
OpenAlexW2769473688

What OpenQuestion holds

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Registered trials

None linked

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.