Evidence map›Paper›PMID 26488607›Full record

ArticlePloS one2015

In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

Sarada Devi Ramachandran, Katharina Schirmer, Bernhard Münst, Stefan Heinz, Shahrouz Ghafoory, Stefan Wölfl, Katja Simon-Keller, Alexander Marx, Cristina Ionica Øie, Matthias P Ebert and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

37 citing papers in PubMed, 109 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. International journal of stem cells · 2023
    Review
  6. Vascularized Tissue Organoids.Bioengineering (Basel, Switzerland) · 2023
    Review
  7. Review
  8. Article
  9. Review
  10. MatriGridBioengineering (Basel, Switzerland) · 2022
    Review
  11. Article
  12. Coordination of iron homeostasis by bone morphogenetic proteins: Current understanding and unanswered questions.Developmental dynamics : an official publication of the American Association of Anatomists · 2022
    Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Synthetic alternatives to Matrigel.Nature reviews. Materials · 2020
    Article
  19. Mechanical Stimulation: A Crucial Element of Organ-on-Chip Models.Frontiers in bioengineering and biotechnology · 2020
    Review
  20. 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

13 authors at 5 institutions in 2 countries.

Sarada Devi RamachandranMedicyte GmbH, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Katharina SchirmerDepartment of Medicine II, Faculty of Medicine at Mannheim, Heidelberg University, Mannheim, Germany.
Bernhard MünstMedicyte GmbH, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Stefan HeinzMedicyte GmbH, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany; upcyte technologies GmbH, Osterfeldstraße 12-14, 22529, Hamburg, Germany.
Shahrouz GhafooryInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Stefan WölflInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Katja Simon-KellerInstitute of Pathology, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany.
Alexander MarxInstitute of Pathology, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany.
Cristina Ionica ØieVascular Biology Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Sykehusgt. 44, N-9037, Tromsø, Norway.
Matthias P EbertDepartment of Medicine II, Faculty of Medicine at Mannheim, Heidelberg University, Mannheim, Germany.
Heike WallesTissue Engineering and Regenerative Medicine, University Wuerzburg, Roentgenring 11, 97070, Würzburg, Germany.
Joris BraspenningMedicyte GmbH, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
Katja Breitkopf-HeinleinDepartment of Medicine II, Faculty of Medicine at Mannheim, Heidelberg University, Mannheim, Germany.
Heidelberg University · DEMedicyte (Germany) · DEUiT The Arctic University of Norway · NOUniversity Medical Centre Mannheim · DEUniversity of Mannheim · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

Indexed as

AdultAlbuminsBioreactorsCadherinsCell DifferentiationCells, CulturedCollagenCytochrome P-450 Enzyme SystemDrug CombinationsEndothelial CellsHepatocytesHumansImmunohistochemistryLamininLiverMesenchymal Stem CellsAlbuminsCadherinsCollagenCytochrome P-450 Enzyme SystemDrug CombinationsLamininmatrigelProteoglycansTJP1 protein, humanZonula Occludens-1 Protein

Identifiers

PMID26488607
PMCPMC4619350
OpenAlexW2167994300

What OpenQuestion holds

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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.