Evidence map›Paper›PMID 38229108›Full record

ArticleStem cell research & therapy2024

Human intestinal organoid-derived PDGFRα + mesenchymal stroma enables proliferation and maintenance of LGR4 + epithelial stem cells.

JunLong Chen, Shinichiro Horiuchi, So Kuramochi, Tomoyuki Kawasaki, Hayato Kawasumi, Saeko Akiyama, Tomoki Arai, Kenichi Morinaga, Tohru Kimura, Tohru Kiyono and 3 more

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
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  8. Roles of PDGF/PDGFR signaling in various organs.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025
    Review
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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 7 institutions in 1 country.

JunLong ChenCenter for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
Shinichiro HoriuchiDivision of Pharmacology, National Institute of Health Sciences, Kawasaki, Japan.
So KuramochiCenter for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
Tomoyuki KawasakiCenter for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
Hayato KawasumiCenter for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
Saeko AkiyamaCenter for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
Tomoki AraiCenter for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
Kenichi Morinaga1st Section, 1st Development Department, Food and Healthcare Business Development Unit, Business Development Division, Research & Business Development Center, Dai Nippon Printing Co., Ltd., Tokyo, Japan.
Tohru KimuraLaboratory of Stem Cell Biology, Department of BioSciences, Kitasato University School of Science, Kanagawa, Japan.
Tohru KiyonoProject for Prevention of HPV-Related Cancer, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.
Hidenori AkutsuCenter for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
Seiichi IshidaDivision of Pharmacology, National Institute of Health Sciences, Kawasaki, Japan.
Akihiro UmezawaCenter for Regenerative Medicine, National Center for Child Health and Development Research Institute, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan. umezawa@1985.jukuin.keio.ac.jp.
National Center For Child Health and Development · JPChiba Cancer Center · JPDai Nippon Printing (Japan) · JPKitasato University · JPNational Institute of Health Sciences · JPSojo University · JPTohoku University · JP

Funding

JST JPMJFS2102
6 · The paper itself

Abstract

backgroundIntestinal epithelial cells derived from human pluripotent stem cells (hPSCs) are generally maintained and cultured as organoids in vitro because they do not exhibit adhesion when cultured. However, the three-dimensional structure of organoids makes their use in regenerative medicine and drug discovery difficult. Mesenchymal stromal cells are found near intestinal stem cells in vivo and provide trophic factors to regulate stem cell maintenance and proliferation, such as BMP inhibitors, WNT, and R-spondin. In this study, we aimed to use mesenchymal stromal cells isolated from hPSC-derived intestinal organoids to establish an in vitro culture system that enables stable proliferation and maintenance of hPSC-derived intestinal epithelial cells in adhesion culture.

methodsWe established an isolation protocol for intestinal epithelial cells and mesenchymal stromal cells from hPSCs-derived intestinal organoids and a co-culture system for these cells. We then evaluated the intestinal epithelial cells and mesenchymal stromal cells' morphology, proliferative capacity, chromosomal stability, tumorigenicity, and gene expression profiles. We also evaluated the usefulness of the cells for pharmacokinetic and toxicity studies.

resultsThe proliferating intestinal epithelial cells exhibited a columnar form, microvilli and glycocalyx formation, cell polarity, and expression of drug-metabolizing enzymes and transporters. The intestinal epithelial cells also showed barrier function, transporter activity, and drug-metabolizing capacity. Notably, small intestinal epithelial stem cells cannot be cultured in adherent culture without mesenchymal stromal cells and cannot replaced by other feeder cells. Organoid-derived mesenchymal stromal cells resemble the trophocytes essential for maintaining small intestinal epithelial stem cells and play a crucial role in adherent culture.

conclusionsThe high proliferative expansion, productivity, and functionality of hPSC-derived intestinal epithelial cells may have potential applications in pharmacokinetic and toxicity studies and regenerative medicine.

Indexed as

Pluripotent Stem CellsReceptor, Platelet-Derived Growth Factor alphaCell DifferentiationCell ProliferationEpithelial CellsHumansIntestinal MucosaOrganoidsReceptors, G-Protein-CoupledLGR4 protein, humanReceptor, Platelet-Derived Growth Factor alphaReceptors, G-Protein-CoupledAdherent cultureEpithelium-mesenchyme co-cultureGREM1Intestinal stem cellsMesenchymeOrganoidsPharmacokineticsPluripotent stem cellsRegenerationTrophocytes

Identifiers

PMID38229108
PMCPMC10792855
OpenAlexW4390953420

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.