Evidence map›Paper›PMID 34099675›Full record

ArticleNature communications2021

Generation of functional liver organoids on combining hepatocytes and cholangiocytes with hepatobiliary connections ex vivo.

Naoki Tanimizu, Norihisa Ichinohe, Yasushi Sasaki, Tohru Itoh, Ryo Sudo, Tomoko Yamaguchi, Takeshi Katsuda, Takafumi Ninomiya, Takashi Tokino, Takahiro Ochiya and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 2% 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

53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.

  1. [Organoid-based strategies and challenges in tissue regeneration].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2026
    Pooled it
  2. Guideline
  3. Review
  4. Article
  5. A 3D In Vitro Model of the Human Hepatobiliary Junction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Preclinical mouse models for studying cholangiocarcinoma.Liver research (Beijing, China) · 2026
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Novel emerging cell and organoid systems for the study of drug metabolism and toxicity in humans.Drug metabolism and disposition: the biological fate of chemicals · 2025
    Review
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

12 authors at 5 institutions in 2 countries.

Naoki TanimizuDepartment of Tissue Development and Regeneration, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. tanimizu@sapmed.ac.jp.ORCID 0000-0001-8167-1401
Norihisa IchinoheDepartment of Tissue Development and Regeneration, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Yasushi SasakiBiology Division, Department of Liberal Arts and Sciences, Center for Medical Education, Sapporo Medical University, Sapporo, Japan.ORCID 0000-0002-3500-8059
Tohru ItohLaboratory of Stem Cell Therapy, The Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.ORCID 0000-0002-6579-1638
Ryo SudoDepartment of System Design Engineering, Keio University, Yokohama, Japan.ORCID 0000-0002-1053-9662
Tomoko YamaguchiDepartment of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Takeshi KatsudaUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0003-3960-033X
Takafumi NinomiyaDepartment of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan.
Takashi TokinoDepartment of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.ORCID 0000-0001-9428-9543
Takahiro OchiyaDepartment of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Atsushi MiyajimaLaboratory of Stem Cell Therapy, The Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
Toshihiro MitakaDepartment of Tissue Development and Regeneration, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Sapporo Medical University · JPThe University of Tokyo · JPTokyo Medical University · JPKeio University · JPUniversity of Pennsylvania · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the liver, the bile canaliculi of hepatocytes are connected to intrahepatic bile ducts lined with cholangiocytes, which remove cytotoxic bile from the liver tissue. Although liver organoids have been reported, it is not clear whether the functional connection between hepatocytes and cholangiocytes is recapitulated in those organoids. Here, we report the generation of a hepatobiliary tubular organoid (HBTO) using mouse hepatocyte progenitors and cholangiocytes. Hepatocytes form the bile canalicular network and secrete metabolites into the canaliculi, which are then transported into the biliary tubular structure. Hepatocytes in HBTO acquire and maintain metabolic functions including albumin secretion and cytochrome P450 activities, over the long term. In this study, we establish functional liver tissue incorporating a bile drainage system ex vivo. HBTO enable us to reproduce the transport of hepatocyte metabolites in liver tissue, and to investigate the way in which the two types of epithelial cells establish functional connections.

Indexed as

AnimalsBile Ducts, IntrahepaticCell CommunicationCell DifferentiationCells, CulturedHepatocytesLiverMiceOrganoidsPrimary Cell CultureStem Cells

Identifiers

PMID34099675
PMCPMC8185093
OpenAlexW3171766833

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.