Evidence map›Paper›PMID 31715015›Full record

ArticleHepatology (Baltimore, Md.)2020

Large-Scale Production of LGR5-Positive Bipotential Human Liver Stem Cells.

Kerstin Schneeberger, Natalia Sánchez-Romero, Shicheng Ye, Frank G van Steenbeek, Loes A Oosterhoff, Iris Pla Palacin, Chen Chen, Monique E van Wolferen, Gilles van Tienderen, Ruby Lieshout and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
14.6field-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

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.

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  7. [Advances in the construction and application of a novel liver organoid model for hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
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22 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

21 authors at 8 institutions in 3 countries.

Kerstin SchneebergerDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.ORCID 0000-0001-8109-7657
Natalia Sánchez-RomeroInstituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
Shicheng YeDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Frank G van SteenbeekDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Loes A OosterhoffDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Iris Pla PalacinInstituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
Chen ChenDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Monique E van WolferenDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Gilles van TienderenDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Ruby LieshoutDepartment of Surgery, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
Haaike Colemonts-VroninksDepartment of In Vitro Toxicology and Dermato-cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
Imre ScheneDivision of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Ruurdtje HoekstraTytgat Institute for Liver and Intestinal Research, Gastroenterology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Monique M A VerstegenDepartment of Surgery, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
Luc J W van der LaanDepartment of Surgery, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
Louis C PenningDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Sabine A FuchsDivision of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
Hans CleversHubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, the Netherlands.
Joery De KockDepartment of In Vitro Toxicology and Dermato-cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.ORCID 0000-0002-4078-4896
Pedro M BaptistaInstituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain.
Bart SpeeDepartment of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Utrecht University · NLErasmus MC · NLInstituto de Investigación Sanitaria Aragón · ESRoyal Netherlands Academy of Arts and Sciences · NLUniversity Medical Center Utrecht · NLVrije Universiteit Brussel · BEAmsterdam UMC Location University of Amsterdam · NLFundacion Agencia Aragonesa para la Investigacion y el Desarrollo · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsThe gap between patients on transplant waiting lists and available donor organs is steadily increasing. Human organoids derived from leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5)-positive adult stem cells represent an exciting new cell source for liver regeneration; however, culturing large numbers of organoids with current protocols is tedious and the level of hepatic differentiation is limited. APPROACH AND

resultsHere, we established a method for the expansion of large quantities of human liver organoids in spinner flasks. Due to improved oxygenation in the spinner flasks, organoids rapidly proliferated and reached an average 40-fold cell expansion after 2 weeks, compared with 6-fold expansion in static cultures. The organoids repopulated decellularized liver discs and formed liver-like tissue. After differentiation in spinner flasks, mature hepatocyte markers were highly up-regulated compared with static organoid cultures, and cytochrome p450 activity reached levels equivalent to hepatocytes.

conclusionsWe established a highly efficient method for culturing large numbers of LGR5-positive stem cells in the form of organoids, which paves the way for the application of organoids for tissue engineering and liver transplantation.

Indexed as

Cell Culture TechniquesCell ProliferationLiver RegenerationLiver TransplantationTissue EngineeringCell DifferentiationCells, CulturedHepatocytesHumansOrganoidsReceptors, G-Protein-CoupledStem CellsLGR5 protein, humanReceptors, G-Protein-Coupled

Identifiers

PMID31715015
PMCPMC7496924
OpenAlexW2988904063

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Registered trials

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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.