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Cited by 295Liver physiology and pathologyCellular Mechanics and InteractionsTissue Engineering and Regenerative Medicine

Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation.

Open access
Dunn, J C, Tompkins, R G, Yarmush, M L·1992·The Journal of cell biology
DOI 10.1083/jcb.116.4.1043PMC PMC2289333
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Abstract

The influence of extracellular matrix configuration on the tissue-specific function of cultured hepatocytes was investigated. Adult rat hepatocytes sandwiched between two layers of collagen gel were compared to cells cultured on a single layer of collagen gel for differences in the total RNA content, the level of albumin-specific mRNA, the rate of albumin gene transcription, and the rate of albumin mRNA translation. Adult hepatocytes in the sandwich system maintained the level of albumin mRNA similar to that found in the normal liver for at least six weeks, whereas the level of albumin mRNA declined rapidly in the single gel system. After one week of culture, hepatocytes in the single gel system could be induced to recover the high level of albumin mRNA and albumin production when a second layer of collagen gel was overlaid at that time. Furthermore, sandwiched hepatocytes maintained significantly higher transcriptional activity compared to cells in the single gel system. In addition to transcriptional control, the ultimate rate of albumin production was shown to depend on the rate of translation, which increased with culture time and reached a plateau in one to two weeks. This increase in translational activity over time in culture was observed in both the sandwich and the single gel systems and, thus, appeared to be independent of the configuration of extracellular matrix.

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Crossref · 10.1083/jcb.116.4.1043

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  • The sandwich culture method has long been demonstrated to produce hepatocyte cell cultures where morphology and function more accurately reproduce in vivo behavior.

    “The sandwich culture method, e.g., placing cells between two layers comprised of ECM, polyacrylamide, or collagen, has long been demonstrated to produce hepatocyte cell cultures, where morphology and function more accurately reproduce in vivo behavior (9,29,34,65,73).”

    From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [29]

    The opening summary (p. 1043) reports that rat hepatocytes between two collagen layers maintained albumin mRNA at levels similar to normal liver, supporting the claim about preserved function. The paper does not demonstrate that sandwich cultures reproduce in vivo morphology more accurately, and it tests collagen rather than the other materials listed in the citing sentence. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Dunn et al. found that sandwich culture maintained proper albumin production rate for at least 6 weeks, whereas the one-gel system had rates tenfold lower than normal by the end of the first week.

    “Their results showed that the sandwich culture could maintain a proper albumin production rate for at least 6 wk, whereas the one-gel system already had rates that were tenfold lower than normal by the end of the first week (29).”

    From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [29]

    The Results (p. 1045) say sandwich cultures maintained albumin production for at least six weeks and that production rates differed roughly tenfold between the sandwich and single-gel systems by the end of week one. The paper does not say the single-gel production rate was tenfold lower than normal; its comparison with normal liver concerns albumin mRNA levels, not production rates. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • The effect of cell polarization in 2D culture can be mitigated using a sandwich culture method that adds a layer of ECM atop the cells to eliminate apical-basal polarity and mimic 3D ECM.

    “The effect of cell polarization in 2D cell culture can be mitigated using a sandwich culture method that adds a layer of ECM atop the cells (9,29,34,65,73) to eliminate apical-basal polarity and provide a mimic of 3D ECM.”

    From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [29]

    The Hepatocyte Culture methods describe adding a second collagen-gel layer over the cells, supporting the sandwich-culture method. But the discussion proposes that this configuration establishes proper cellular polarity, with two basolateral surfaces separated by an apical belt—not that it eliminates apical-basal polarity. The passages do not explicitly characterize it as a mimic of 3D ECM; page numbers were not supplied. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • In 2D cultures, there are decreases in transcriptional genes and rapid changes in morphology.

    “In 2D cultures, there are decreases in transcriptional genes and rapid changes in morphology (29,34).”

    From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [29]

    The Results (p. 1047) show that albumin-gene transcription declined over seven days in hepatocytes cultured on a single collagen gel. The Discussion (p. 1050) mentions a change in actin-filament organization when hepatocytes are sandwiched between collagen gels, but does not establish rapid morphological changes in the single-gel culture. The claim also generalizes a finding about specific genes in rat hepatocytes to 2D cultures broadly. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Conventional 2D culture methods, flasks with or without ECM protein coatings, do not establish well enough the complex microenvironment that hepatocytes need to function.

    “Hepatocytes in the liver are surrounded by a complex ECM, and several researchers have shown that conventional 2D culture methods, flasks with or without ECM protein coatings, do not establish well enough the complex microenvironment that hepatocytes need to function (29,34,73).”

    From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [29]

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Related

Authors
Dunn, J. C., Tompkins, R. G., & Yarmush, M. L.
Affiliations
Harvard University (US)
ORCID
Venue
The Journal of cell biology
Publisher
Rockefeller University Press
Published
1992-02-15
Volume
116
Issue
4
Pages
1043-1053
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.116.4.1043
PMC
PMC2289333
OpenAlex
W2067188612
Cited by
295
References
52
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 10 · 2018: 9 · 2017: 4 · 2016: 8 · 2015: 14 · 2014: 8 · 2013: 6 · 2012: 3
FWCI
8.43
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk041709-05, 5k08dk001746-05)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-01746, R01 DK-41709)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
hepatocytes, albumin synthesis, tissue-specific gene expression, hepatocyte culture
MeSH terms
Albumins, Animals, Cells, Cultured, Collagen, Extracellular Matrix, Female, Gene Expression Regulation, Kinetics, Liver, Rats, Inbred Lew, RNA, Messenger, Transcription, Genetic, Protein Biosynthesis, Rats

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