Evidence map›Paper›PMID 27296616›Full record

ArticleLab on a chip2016

Engineering a perfusable 3D human liver platform from iPS cells.

Arnout Schepers, Cheri Li, Arnav Chhabra, Benjamin Tschudy Seney, Sangeeta Bhatia

Abstract read
In one paragraph

Article in Lab on a chip, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

71 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Review
  7. Lessons Learned from Liver-on-Chip Platform.Annals of biomedical engineering · 2025
    Review
  8. Review
  9. Review
  10. Modeling the Effects of Protracted Cosmic Radiation in a Human Organ-on-Chip Platform.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  11. Review
  12. Review
  13. Article
  14. Engineered organoids for biomedical applications.Advanced drug delivery reviews · 2023
    Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article

11 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

5 authors.

Arnout SchepersKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. sbhatia@mit.edu and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cheri LiKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. sbhatia@mit.edu and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Arnav ChhabraKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. sbhatia@mit.edu and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Benjamin Tschudy SeneyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. sbhatia@mit.edu and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sangeeta BhatiaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. sbhatia@mit.edu and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA and Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USA and Howard Hughes Medical Institute, Cambridge, MA 02139, USA.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Tissue Chips for Rare Disease: Adding Timothy Syndrome to the HeLIVaSkCa platformUH3EB017103 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2014 to 2016
$7.1M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NIBIB NIH HHS UH3 EB017103
6 · The paper itself

Abstract

In vitro models of human tissue are crucial to our ability to study human disease as well as develop safe and effective drug therapies. Models of single organs in static and microfluidic culture have been established and shown utility for modeling some aspects of health and disease; however, these systems lack multi-organ interactions that are critical to some aspects of drug metabolism and toxicity. Thus, as part of a consortium of researchers, we have developed a liver chip that meets the following criteria: (1) employs human iPS cells from a patient of interest, (2) cultures cells in perfusable 3D organoids, and (3) is robust to variations in perfusion rate so as to be compatible in series with other specialized tissue chips (e.g. heart, lung). In order to achieve this, we describe methods to form hepatocyte aggregates from primary and iPS-derived cells, alone and in co-culture with support cells. This necessitated a novel culture protocol for the interrupted differentiation of iPS cells that permits their removal from a plated surface and aggregation while maintaining phenotypic hepatic functions. In order to incorporate these 3D aggregates in a perfusable platform, we next encapsulated the cells in a PEG hydrogel to prevent aggregation and overgrowth once on chip. We adapted a C-trap chip architecture from the literature that enabled robust loading with encapsulated organoids and culture over a range of flow rates. Finally, we characterize the liver functions of this iHep organoid chip under perfusion and demonstrate a lifetime of at least 28 days. We envision that such this strategy can be generalized to other microfluidic tissue models and provides an opportunity to query patient-specific liver responses in vitro.

Indexed as

AlbuminsCell DifferentiationCoculture TechniquesCytochrome P-450 Enzyme SystemHepatocytesHumansInduced Pluripotent Stem CellsLab-On-A-Chip DevicesLiverPerfusionTissue EngineeringAlbuminsCytochrome P-450 Enzyme System

Identifiers

PMID27296616
PMCPMC5318999

What OpenQuestion holds

Textmetadata
LicenceTDM
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.