Evidence map›Paper›PMID 30004612›Full record

ArticleStem cells (Dayton, Ohio)2018

Human-Induced Pluripotent Stem Cells Generate Light Responsive Retinal Organoids with Variable and Nutrient-Dependent Efficiency.

Dean Hallam, Gerrit Hilgen, Birthe Dorgau, Lili Zhu, Min Yu, Sanja Bojic, Philip Hewitt, Michael Schmitt, Marianne Uteng, Stefan Kustermann and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
8.0field-weighted citation impact, top 2% 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

129 citing papers in PubMed, 198 citations in OpenAlex.

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  11. International journal of molecular sciences · 2025
    Article
  12. Single-Cell Transcriptomics onBiomedicines · 2025
    Article
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  17. Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration.International journal of molecular sciences · 2025
    Review
  18. Review
  19. Review
  20. Article

69 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

18 authors at 5 institutions in 3 countries.

Dean HallamNewcastle University, Institute for Genetic Medicine, Newcastle upon Tyne, UK.
Gerrit HilgenNewcastle University, Institute of Neuroscience, Newcastle upon Tyne, UK.
Birthe DorgauNewcastle University, Institute for Genetic Medicine, Newcastle upon Tyne, UK.
Lili ZhuNewcastle University, Institute for Genetic Medicine, Newcastle upon Tyne, UK.
Min YuNewcastle University, Institute for Genetic Medicine, Newcastle upon Tyne, UK.
Sanja BojicNewcastle University, Institute for Genetic Medicine, Newcastle upon Tyne, UK.
Philip HewittMerck KGaA, Darmstadt, Germany.
Michael SchmittMerck KGaA, Darmstadt, Germany.
Marianne UtengNovartis, Basel, Switzerland.
Stefan KustermannF. Hoffmann-La Roche Ltd, University of Tübingen, Basel, Switzerland.
David SteelNewcastle University, Institute for Genetic Medicine, Newcastle upon Tyne, UK.
Mike NicholdsNewcells Biotech, Newcastle upon Tyne, UK.
Robert ThomasCentre for Biological Engineering, Loughborough University, Loughborough, UK.
Achim TreumannNewcastle University, Newcastle University Protein and Proteome Analysis, Newcastle upon Tyne, UK.
Andrew PorterNewcastle University, Newcastle University Protein and Proteome Analysis, Newcastle upon Tyne, UK.
Evelyne SernagorNewcastle University, Institute of Neuroscience, Newcastle upon Tyne, UK.
Lyle ArmstrongNewcastle University, Institute for Genetic Medicine, Newcastle upon Tyne, UK.
Majlinda LakoNewcastle University, Institute for Genetic Medicine, Newcastle upon Tyne, UK.ORCID 0000-0003-1327-8573
Newcastle University · GBMerck (Germany) · DELoughborough University · GBNovartis (Switzerland) · CHRoche (Switzerland) · CH

Funding

European Research Council 614620Medical Research Council MC_PC_15030Medical Research Council MR/R011338/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/C016106/1
6 · The paper itself

Abstract

The availability of in vitro models of the human retina in which to perform pharmacological and toxicological studies is an urgent and unmet need. An essential step for developing in vitro models of human retina is the ability to generate laminated, physiologically functional, and light-responsive retinal organoids from renewable and patient specific sources. We investigated five different human-induced pluripotent stem cell (iPSC) lines and showed a significant variability in their efficiency to generate retinal organoids. Despite this variability, by month 5 of differentiation, all iPSC-derived retinal organoids were able to generate light responses, albeit immature, comparable to the earliest light responses recorded from the neonatal mouse retina, close to the period of eye opening. All iPSC-derived retinal organoids exhibited at this time a well-formed outer nuclear like layer containing photoreceptors with inner segments, connecting cilium, and outer like segments. The differentiation process was highly dependent on seeding cell density and nutrient availability determined by factorial experimental design. We adopted the differentiation protocol to a multiwell plate format, which enhanced generation of retinal organoids with retinal-pigmented epithelium (RPE) and improved ganglion cell development and the response to physiological stimuli. We tested the response of iPSC-derived retinal organoids to Moxifloxacin and showed that similarly to in vivo adult mouse retina, the primary affected cell types were photoreceptors. Together our data indicate that light responsive retinal organoids derived from carefully selected and differentiation efficient iPSC lines can be generated at the scale needed for pharmacology and drug screening purposes. Stem Cells 2018;36:1535-1551.

Indexed as

AdultAgedAged, 80 and overAnimalsCell DifferentiationFemaleHumansInduced Pluripotent Stem CellsMaleMiceNutrientsOrganoidsRetinaNutrientsiPSRetinaRetinal photoreceptorsStem cells

Identifiers

PMID30004612
PMCPMC6392112
OpenAlexW2882986564

What Socratic holds

Textmetadata
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 Socratic graph.