Evidence map›Paper›PMID 27851739›Full record

ArticleNature2016

Designer matrices for intestinal stem cell and organoid culture.

Nikolce Gjorevski, Norman Sachs, Andrea Manfrin, Sonja Giger, Maiia E Bragina, Paloma Ordóñez-Morán, Hans Clevers, Matthias P Lutolf

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 760 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
760citing papers in PubMed, 2 pooled it
52.8field-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

760 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,364 citations in OpenAlex.

  1. Guiding Principles: Reporting Elements for Gastrointestinal Organoid Research.Cellular and molecular gastroenterology and hepatology · 2026
    Guideline
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700 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Nikolce GjorevskiLaboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Norman SachsHubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
Andrea ManfrinLaboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Sonja GigerLaboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Maiia E BraginaLaboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Paloma Ordóñez-MoránSwiss Institute for Experimental Cancer Research (ISREC), EPFL, Lausanne, Switzerland.
Hans CleversHubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands.
Matthias P LutolfLaboratory of Stem Cell Bioengineering, Institute of Bioengineering, School of Life Sciences (SV) and School of Engineering (STI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
École Polytechnique Fédérale de Lausanne · CHHubrecht Institute for Developmental Biology and Stem Cell Research · NLUniversity Medical Center Utrecht · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epithelial organoids recapitulate multiple aspects of real organs, making them promising models of organ development, function and disease. However, the full potential of organoids in research and therapy has remained unrealized, owing to the poorly defined animal-derived matrices in which they are grown. Here we used modular synthetic hydrogel networks to define the key extracellular matrix (ECM) parameters that govern intestinal stem cell (ISC) expansion and organoid formation, and show that separate stages of the process require different mechanical environments and ECM components. In particular, fibronectin-based adhesion was sufficient for ISC survival and proliferation. High matrix stiffness significantly enhanced ISC expansion through a yes-associated protein 1 (YAP)-dependent mechanism. ISC differentiation and organoid formation, on the other hand, required a soft matrix and laminin-based adhesion. We used these insights to build a fully defined culture system for the expansion of mouse and human ISCs. We also produced mechanically dynamic matrices that were initially optimal for ISC expansion and subsequently permissive to differentiation and intestinal organoid formation, thus creating well-defined alternatives to animal-derived matrices for the culture of mouse and human stem-cell-derived organoids. Our approach overcomes multiple limitations of current organoid cultures and greatly expands their applicability in basic and clinical research. The principles presented here can be extended to identify designer matrices that are optimal for long-term culture of other types of stem cells and organoids.

Indexed as

AnimalsCell AdhesionCell Culture TechniquesCell DifferentiationCell LineageCell ProliferationCell ShapeExtracellular MatrixFibronectinsHumansHydrogel, Polyethylene Glycol DimethacrylateIntestinesMiceOrganoidsProteolysisStem Cell NicheFibronectinsHydrogel, Polyethylene Glycol Dimethacrylate

Identifiers

PMID27851739
OpenAlexW2552754421

What OpenQuestion holds

Textmetadata
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.