Evidence map›Paper›PMID 32290899›Full record

ArticleGene expression2020

Microscale Collagen and Fibroblast Interactions Enhance Primary Human Hepatocyte Functions in Three-Dimensional Models.

David A Kukla, Alexandra L Crampton, David K Wood, Salman R Khetani

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gene expression, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
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  13. [Long term maintenance of cytochrome P450 activity in a cell sheet-based three-dimensional human hepatic model].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2022
    Article
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  15. Bioengineering of the liver.APL bioengineering · 2022
    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

4 authors at 2 institutions in 1 country.

David A KuklaDepartment of Bioengineering, University of Illinois at ChicagoChicago, ILUSA.
Alexandra L CramptonDepartment of Biomedical Engineering, University of MinnesotaMinneapolis, MNUSA.
David K WoodDepartment of Biomedical Engineering, University of MinnesotaMinneapolis, MNUSA.
Salman R KhetaniDepartment of Bioengineering, University of Illinois at ChicagoChicago, ILUSA.
University of Illinois Chicago · USUniversity of Minnesota · US

Funding

Synergistic effects of ECM and heterotypic crosstalk on cellular responses in non-alcoholic fatty liver diseaseR01DK115747 · NIDDK · UNIVERSITY OF ILLINOIS AT CHICAGO · PI Salman R Khetani, Gregory H Underhill · 2018 to 2026
$3.7M
Functionally maturing iPSC-derived human hepatocytes in 3D microgelsR21ES027622 · NIEHS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI KHETANI, SALMAN R · 2017 to 2018
$427k
NIDDK NIH HHS R01 DK115747NIEHS NIH HHS R21 ES027622
6 · The paper itself

Abstract

Human liver models that are three-dimensional (3D) in architecture are indispensable for compound metabolism/toxicity screening, to model liver diseases for drug discovery, and for cell-based therapies; however, further development of such models is needed to maintain high levels of primary human hepatocyte (PHH) functions for weeks to months. Therefore, here we determined how microscale 3D collagen I presentation and fibroblast interaction affect the longevity of PHHs. High-throughput droplet microfluidics was utilized to generate reproducibly sized (∼300-μm diameter) microtissues containing PHHs encapsulated in collagen I ± supportive fibroblasts, namely, 3T3-J2 murine embryonic fibroblasts or primary human hepatic stellate cells (HSCs); self-assembled spheroids and bulk collagen gels (macrogels) containing PHHs served as controls. Hepatic functions and gene expression were subsequently measured for up to 6 weeks. We found that microtissues placed within multiwell plates rescued PHH functions at 2- to 30-fold higher levels than spheroids or macrogels. Further coating of PHH microtissues with 3T3-J2s led to higher hepatic functions than when the two cell types were either coencapsulated together or when HSCs were used for the coating instead. Importantly, the 3T3-J2-coated PHH microtissues displayed 6+ weeks of relatively stable hepatic gene expression and function at levels similar to freshly thawed PHHs. Lastly, microtissues responded in a clinically relevant manner to drug-mediated cytochrome P450 induction or hepatotoxicity. In conclusion, fibroblast-coated collagen microtissues containing PHHs display high hepatic functions for 6+ weeks and are useful for assessing drug-mediated CYP induction and hepatotoxicity. Ultimately, microtissues may find utility for modeling liver diseases and as building blocks for cell-based therapies.

Indexed as

Cell Encapsulation3T3 CellsAnimalsCells, CulturedCoculture TechniquesCollagen Type ICytochrome P-450 Enzyme SystemEnzyme InductionGelsGene ExpressionHepatic Stellate CellsHepatocytesHumansLab-On-A-Chip DevicesMiceOmeprazoleCollagen Type ICytochrome P-450 Enzyme SystemGelsOmeprazoleRifampin

Identifiers

PMID32290899
PMCPMC7284102
OpenAlexW3015983535

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.