Evidence map›Paper›PMID 27240736›Full record

ArticleScientific reports2016

A Microfabricated Platform for Generating Physiologically-Relevant Hepatocyte Zonation.

William J McCarty, O Berk Usta, Martin L Yarmush

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

34 citing papers in PubMed, 65 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Liver Regeneration and Immunity: A Tale to Tell.International journal of molecular sciences · 2023
    Review
  12. Review
  13. Review
  14. Review
  15. Microtechnology-basedAPL bioengineering · 2021
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
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

3 authors at 1 institution in 1 country.

William J McCartyCenter for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children-Boston, Boston, MA, USA.
O Berk UstaCenter for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children-Boston, Boston, MA, USA.
Martin L YarmushCenter for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Hospitals for Children-Boston, Boston, MA, USA.
Harvard University · US

Funding

Bio-MicroElectroMechanical Systems Resource CenterP41EB002503 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI TONER, MEHMET · 2004 to 2018
$17.4M
Collaborations to Extend the Microphysiology Database for Multiple Organ Models,UH2TR000503 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAYLOR, D. LANSING, YARMUSH, MARTIN L · 2012 to 2013
$2.3M
Novel Microfluidic Platforms for Actively Controlled in-vitro Liver ZonationR21EB020192 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI USTA, OSMAN BERK · 2015 to 2016
$479k
Hepatic zonation in a microfluidic liver model: application to drug metabolismF32DK098905 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MCCARTY, WILLIAM JOSEPH · 2013 to 2015
$162k
NCATS NIH HHS UH2 TR000503NIBIB NIH HHS P41 EB002503NIBIB NIH HHS R21 EB020192NIDDK NIH HHS F32 DK098905
6 · The paper itself

Abstract

In vitro liver models have been important tools for more than 40 years for academic research and preclinical toxicity screening by the pharmaceutical industry. Hepatocytes, the highly metabolic parenchymal cells of the liver, are efficient at different metabolic chemistries depending on their relative spatial location along the sinusoid from the portal triad to the central vein. Although replicating hepatocyte metabolic zonation is vitally important for physiologically-relevant in vitro liver tissue and organ models, it is most often completely overlooked. Here, we demonstrate the creation of spatially-controlled zonation across multiple hepatocyte metabolism levels through the application of precise concentration gradients of exogenous hormone (insulin and glucagon) and chemical (3-methylcholanthrene) induction agents in a microfluidic device. Observed gradients in glycogen storage via periodic acid-Schiff staining, urea production via carbamoyl phosphatase synthetase I staining, and cell viability after exposure to allyl alcohol and acetaminophen demonstrated the in vitro creation of hepatocyte carbohydrate, nitrogen, alcohol degradation, and drug conjugation metabolic zonation. This type of advanced control system will be crucial for studies evaluating drug metabolism and toxicology using in vitro constructs.

Indexed as

AcetaminophenAnimalsCell Culture TechniquesCells, CulturedEthanolFemaleGlucagonGlucoseHepatocytesInsulinLab-On-A-Chip DevicesMethylcholanthreneMicrotechnologyNitrogenRats, Inbred LewAcetaminophenEthanolGlucagonGlucoseInsulinMethylcholanthreneNitrogen

Identifiers

PMID27240736
PMCPMC4886516
OpenAlexW2415956675

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.