Evidence map›Paper›PMID 29675458›Full record

ReviewCellular and molecular gastroenterology and hepatology2018

Bioengineered Liver Models for Drug Testing and Cell Differentiation Studies.

Gregory H Underhill, Salman R Khetani

Open access · goldAbstract readReview
In one paragraph

Review 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 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
9.3field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 171 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Lessons Learned from Liver-on-Chip Platform.Annals of biomedical engineering · 2025
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025
    Review
  11. Article
  12. [Liver organoid technology and its related progress in liver disease research].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025
    Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

7 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 1 country.

Gregory H UnderhillDepartment of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois.
Salman R KhetaniDepartment of Bioengineering, University of Illinois at Chicago, Chicago, Illinois.
University of Illinois Chicago · USUniversity of Illinois Urbana-Champaign · 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
Cooperative roles of Notch and biomechanics in biliary differentiationR03EB022254 · NIBIB · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI UNDERHILL, GREGORY H · 2016 to 2017
$150k
NIBIB NIH HHS R03 EB022254NIEHS NIH HHS R21 ES027622
6 · The paper itself

Abstract

In vitro models of the human liver are important for the following: (1) mitigating the risk of drug-induced liver injury to human beings, (2) modeling human liver diseases, (3) elucidating the role of single and combinatorial microenvironmental cues on liver cell function, and (4) enabling cell-based therapies in the clinic. Methods to isolate and culture primary human hepatocytes (PHHs), the gold standard for building human liver models, were developed several decades ago; however, PHHs show a precipitous decline in phenotypic functions in 2-dimensional extracellular matrix-coated conventional culture formats, which does not allow chronic treatment with drugs and other stimuli. The development of several engineering tools, such as cellular microarrays, protein micropatterning, microfluidics, biomaterial scaffolds, and bioprinting, now allow precise control over the cellular microenvironment for enhancing the function of both PHHs and induced pluripotent stem cell-derived human hepatocyte-like cells; long-term (4+ weeks) stabilization of hepatocellular function typically requires co-cultivation with liver-derived or non-liver-derived nonparenchymal cell types. In addition, the recent development of liver organoid culture systems can provide a strategy for the enhanced expansion of therapeutically relevant cell types. Here, we discuss advances in engineering approaches for constructing in vitro human liver models that have utility in drug screening and for determining microenvironmental determinants of liver cell differentiation/function. Design features and validation data of representative models are presented to highlight major trends followed by the discussion of pending issues that need to be addressed. Overall, bioengineered liver models have significantly advanced our understanding of liver function and injury, which will prove useful for drug development and ultimately cell-based therapies.

Indexed as

3D, 3-dimensionalBAL, bioartificial liverBioprintingCellular MicroarraysCRP, C-reactive proteinCYP450, cytochrome P450DILI, drug-induced liver injuryECM, extracellular matrixHepatocytesHSC, hepatic stellate celliHep, induced pluripotent stem cell-derived human hepatocyte-like cellIL, interleukiniPS, induced pluripotent stemKC, Kupffer cellLSEC, liver sinusoidal endothelial cellMicrofluidicsMicropatterned Co-CulturesMPCC, micropatterned co-cultureNPC, nonparenchymal cellPEG, polyethylene glycolPHH, primary human hepatocyteSpheroids

Identifiers

PMID29675458
PMCPMC5904032
OpenAlexW2771920343

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.