Evidence map›Paper›PMID 33222247›Full record

ReviewHepatology (Baltimore, Md.)2021

Organoids and Spheroids as Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma.

Keisaku Sato, Wenjun Zhang, Samira Safarikia, Abdulkadir Isidan, Angela M Chen, Ping Li, Heather Francis, Lindsey Kennedy, Leonardo Baiocchi, Domenico Alvaro and 3 more

Open access · greenAbstract readReview
In one paragraph

Review in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 2 pooled it
7.1field-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

48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Preclinical mouse models for studying cholangiocarcinoma.Liver research (Beijing, China) · 2026
    Review
  7. Article
  8. Modeling ischemic-type biliary lesionFrontiers in bioengineering and biotechnology · 2026
    Article
  9. Review
  10. Article
  11. Development and Validation of a Scaffold-Free Human Multilineage Spheroid Model for Early Stage Cholangiopathies Driven by Cholangiocyte Senescence.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Harnessing Organoid Platforms for Nanoparticle Drug Development.Drug design, development and therapy · 2025
    Review
  19. Organoids in biliary atresia.World journal of pediatric surgery · 2025
    Review
  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

13 authors at 5 institutions in 2 countries.

Keisaku SatoDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0001-5380-8001
Wenjun ZhangDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0001-9801-0634
Samira SafarikiaDepartment of Precision and Translational Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0002-7254-0634
Abdulkadir IsidanDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0001-6655-1268
Angela M ChenDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0001-6716-2088
Ping LiDivision of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0003-1055-9505
Heather FrancisDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0002-3466-3545
Lindsey KennedyDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0001-9224-8940
Leonardo BaiocchiLiver Unit, Department of Medicine, University of Rome Tor Vergata, Rome, Italy.ORCID 0000-0003-3672-4505
Domenico AlvaroDepartment of Precision and Translational Medicine, Sapienza University of Rome, Rome, Italy.ORCID 0000-0003-3771-9644
Shannon GlaserDepartment of Medical Physiology, Texas A&M University, Bryan, TX.ORCID 0000-0002-0749-773X
Burcin Ekser *Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0003-0741-8007
Gianfranco Alpini *Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0002-6658-3021
Indiana University School of MedicineRichard L. Roudebush VA Medical Center · USSapienza University of Rome · ITTexas A&M Health Science Center · USUniversity of Rome Tor Vergata · IT

Funding

Indiana Clinical and Translational Sciences InstituteUL1TR001108 · NCATS · INDIANA UNIVERSITY INDIANAPOLIS · PI DENNE, SCOTT C., SHEKHAR, ANANTHA · 2013 to 2017
$23.3M
The Paracrine Regulation of Mast Cells During Biliary/Cholangiocyte Repair and DamageR01DK108959 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI FRANCIS, HEATHER L · 2016 to 2024
$2.5M
Alcohol-induced hepatotoxicity - implications of secretin/secretin receptor axisR01AA028711 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI ALPINI, GIANFRANCO D, GLASER, SHANNON STROUD · 2020 to 2023
$2.2M
Regulation of Bile Duct Growth in Bile Duct Ligated RatsR01DK062975 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ALPINI, GIANFRANCO D, GLASER, SHANNON STROUD · 2005 to 2014
$1.9M
Role of Sensory Neuropeptides in the Regulation of Biliary FunctionR01DK076898 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ALPINI, GIANFRANCO D, GLASER, SHANNON STROUD · 2008 to 2016
$1.8M
The Role of Stem Cell Derived Microvesicles in Cholestatic Liver InjuryR01DK107310 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ALPINI, GIANFRANCO D, GLASER, SHANNON STROUD · 2015 to 2019
$1.7M
Mechanisms of mast cell/cholangiocyte regulation of non-alcoholic fatty liver disease progressionR01DK119421 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI FRANCIS, HEATHER L · 2019 to 2022
$1.4M
Neuroendocrine Regulation of Biliary Growth and FibrosisR01DK110035 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI ALPINI, GIANFRANCO D, GLASER, SHANNON STROUD · 2017 to 2020
$1.2M
REGULATION OF CELLULAR SENESCENCE BY NON-CODING RNAS IN ALCOHOLIC LIVER INJURYR21AA025997 · NIAAA · SCOTT AND WHITE MEMORIAL HOSPITAL · PI ALPINI, GIANFRANCO D, MENG, FANYIN · 2017 to 2018
$435k
Mechanisms of synergistic regulation of biliary inflammation and fibrosisI01BX003031 · VA · RLR VA MEDICAL CENTER · PI FRANCIS, HEATHER L · 2016 to 2023
–
Autocrine/Paracrine Regulation of Intrahepatic Bile Duct GrowthI01BX000574 · VA · RLR VA MEDICAL CENTER · PI ALPINI, GIANFRANCO D · 2009 to 2022
–
BLR&D Research Career Scientist AwardIK6BX004601 · VA · RLR VA MEDICAL CENTER · PI ALPINI, GIANFRANCO D · 2019 to 2025
–
BLRD VA I01 BX000574BLRD VA I01 BX003031BLRD VA IK6 BX004601BLRD VA IK6 BX005226NCATS NIH HHS UL1 TR001108NIAAA NIH HHS R01 AA028711NIAAA NIH HHS R21 AA025997NIDDK NIH HHS R01 DK062975NIDDK NIH HHS R01 DK076898NIDDK NIH HHS R01 DK107310NIDDK NIH HHS R01 DK108959NIDDK NIH HHS R01 DK110035NIDDK NIH HHS R01 DK119421
6 · The paper itself

Abstract

Cholangiopathies, such as primary sclerosing cholangitis, biliary atresia, and cholangiocarcinoma, have limited experimental models. Not only cholangiocytes but also other hepatic cells including hepatic stellate cells and macrophages are involved in the pathophysiology of cholangiopathies, and these hepatic cells orchestrate the coordinated response against diseased conditions. Classic two-dimensional monolayer cell cultures do not resemble intercellular cell-to-cell interaction and communication; however, three-dimensional cell culture systems, such as organoids and spheroids, can mimic cellular interaction and architecture between hepatic cells. Previous studies have demonstrated the generation of hepatic or biliary organoids/spheroids using various cell sources including pluripotent stem cells, hepatic progenitor cells, primary cells from liver biopsies, and immortalized cell lines. Gene manipulation, such as transfection and transduction can be performed in organoids, and established organoids have functional characteristics which can be suitable for drug screening. This review summarizes current methodologies for organoid/spheroid formation and a potential for three-dimensional hepatic cell cultures as in vitro models of cholangiopathies.

Indexed as

Bile Duct NeoplasmsBile Ducts, IntrahepaticBiliary AtresiaCell CommunicationCell LineCholangiocarcinomaCholangitis, SclerosingHepatic Stellate CellsHepatocytesHumansLiverMacrophagesOrganoidsPluripotent Stem CellsPrimary Cell CultureSpheroids, Cellular

Identifiers

PMID33222247
PMCPMC8529583
OpenAlexW3106635565

What OpenQuestion holds

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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.