Evidence map›Paper›PMID 34063948›Full record

ArticleCells2021

Tissue-Specific Microparticles Improve Organoid Microenvironment for Efficient Maturation of Pluripotent Stem-Cell-Derived Hepatocytes.

Ensieh Zahmatkesh, Mohammad Hossein Ghanian, Ibrahim Zarkesh, Zahra Farzaneh, Majid Halvaei, Zahra Heydari, Farideh Moeinvaziri, Amnah Othman, Marc Ruoß, Abbas Piryaei and 6 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.2field-weighted citation impact, top 6% 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

23 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Organoids for disease modeling and treatment: state-of-the-art.Experimental hematology & oncology · 2026
    Review
  5. Functional Liver Cell-Based Platforms in Biomedical Research.Pharmacology research & perspectives · 2025
    Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Narrative engineering of the liver.Current opinion in genetics & development · 2022
    Review
  19. Article
  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

16 authors at 6 institutions in 4 countries.

Ensieh ZahmatkeshDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.ORCID 0000-0001-9064-3306
Mohammad Hossein GhanianDepartment of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
Ibrahim ZarkeshDepartment of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
Zahra FarzanehDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.ORCID 0000-0001-5234-9026
Majid HalvaeiDepartment of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
Zahra HeydariDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
Farideh MoeinvaziriDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
Amnah OthmanDepartment of Traumatology, Siegfried Weller Institute, University of Tübingen, 72076 Tübingen, Germany.ORCID 0000-0002-0838-9749
Marc RuoßDepartment of Traumatology, Siegfried Weller Institute, University of Tübingen, 72076 Tübingen, Germany.ORCID 0000-0002-0193-4425
Abbas PiryaeiDepartment of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717443, Iran.ORCID 0000-0002-3182-6214
Roberto GramignoliDivision of Pathology, Department of Laboratory Medicine, Karolinska Institutet, 17177 Stockholm, Sweden.ORCID 0000-0003-3362-4170
Saeed YakhkeshiDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
Andreas NüsslerDepartment of Traumatology, Siegfried Weller Institute, University of Tübingen, 72076 Tübingen, Germany.ORCID 0000-0002-6666-6791
Mustapha NajimiLaboratory of Pediatric Hepatology and Cell Therapy, Institute of Experimental & Clinical Research, Université Catholique de Louvain, B-1200 Brussels, Belgium.ORCID 0000-0002-7329-9635
Hossein BaharvandDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.
Massoud VosoughDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.ORCID 0000-0001-5924-4366
Royan Institute · IRUniversity of Science and Culture · IRUniversity of Tübingen · DEKarolinska Institutet · SEShahid Beheshti University of Medical Sciences · IRUCLouvain · BE

Funding

Iran National Science Foundation 96001316Ministry of Health and Medical Education 56700/147National Institute for Medical Research Development 940231 and 982403Royan Institute 96000182
6 · The paper itself

Abstract

Liver organoids (LOs) are receiving considerable attention for their potential use in drug screening, disease modeling, and transplantable constructs. Hepatocytes, as the key component of LOs, are isolated from the liver or differentiated from pluripotent stem cells (PSCs). PSC-derived hepatocytes are preferable because of their availability and scalability. However, efficient maturation of the PSC-derived hepatocytes towards functional units in LOs remains a challenging subject. The incorporation of cell-sized microparticles (MPs) derived from liver extracellular matrix (ECM), could provide an enriched tissue-specific microenvironment for further maturation of hepatocytes inside the LOs. In the present study, the MPs were fabricated by chemical cross-linking of a water-in-oil dispersion of digested decellularized sheep liver. These MPs were mixed with human PSC-derived hepatic endoderm, human umbilical vein endothelial cells, and mesenchymal stromal cells to produce homogenous bioengineered LOs (BLOs). This approach led to the improvement of hepatocyte-like cells in terms of gene expression and function, CYP activities, albumin secretion, and metabolism of xenobiotics. The intraperitoneal transplantation of BLOs in an acute liver injury mouse model led to an enhancement in survival rate. Furthermore, efficient hepatic maturation was demonstrated after ex ovo transplantation. In conclusion, the incorporation of cell-sized tissue-specific MPs in BLOs improved the maturation of human PSC-derived hepatocyte-like cells compared to LOs. This approach provides a versatile strategy to produce functional organoids from different tissues and offers a novel tool for biomedical applications.

Indexed as

HepatocytesLiverOrganoidsAnimalsCell DifferentiationHuman Embryonic Stem CellsHumansHuman Umbilical Vein Endothelial CellsInduced Pluripotent Stem CellsMesenchymal Stem CellsSheephepatic differentiationliver organoidpluripotent stem celltissue engineeringtissue-specific microparticle

Identifiers

PMID34063948
PMCPMC8224093
OpenAlexW3161498706

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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.