Evidence map›Paper›PMID 31670434›Full record

ArticleStem cells (Dayton, Ohio)2020

Developing a simple method to enhance the generation of cone and rod photoreceptors in pluripotent stem cell-derived retinal organoids.

Darin Zerti, Birthe Dorgau, Majed Felemban, Ali E Ghareeb, Min Yu, Yuchun Ding, Natalio Krasnogor, Majlinda Lako

Open access · hybridAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

36 citing papers in PubMed, 56 citations in OpenAlex.

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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

8 authors at 2 institutions in 2 countries.

Darin ZertiInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Birthe DorgauInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Majed FelembanInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Ali E GhareebInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Min YuInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
Yuchun DingInterdisciplinary Computing and Complex Biosystems (ICOS) Research Group, Newcastle University, Newcastle upon Tyne, UK.
Natalio KrasnogorInterdisciplinary Computing and Complex Biosystems (ICOS) Research Group, Newcastle University, Newcastle upon Tyne, UK.
Majlinda LakoInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.ORCID 0000-0003-1327-8573
Newcastle University · GBKing Abdulaziz University · SA

Funding

Biotechnology and Biological Sciences Research Council BB/I02333X/1Medical Research Council MC_PC_15030Medical Research Council MR/N005872/1Medical Research Council MR/T017503/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/C016106/1
6 · The paper itself

Abstract

Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases such as Stargardt's disease, age-related macular degeneration, and retinitis pigmentosa. The final impact of all retinal dystrophies is the loss of photoreceptors; hence, there is a pressing need for research into replacement. Seminal work has shown that a simple three-dimensional culture system enables differentiation of human pluripotent stem cells to retinal organoids containing large numbers of photoreceptors developing alongside retinal neurons and Müller glia cells in a laminated structure that resembles the native retina. Despite these promising developments, current protocols show different efficiencies across pluripotent stem cells and result in retinal organoids with a mixture of photoreceptor cells at varying maturation states, along with nonphotoreceptor cell types. In this study, we investigated the impact of stage-specific addition of retinoic acid (RA), 9-cis-retinal, 11-cis-retinal, levodopa (l-DOPA), triiodothyronine (T3), and γ-secretase inhibitor ((2S)-N-[(3,5-Difluorophenyl)acetyl]-l-alanyl-2-phenyl]glycine1,1-dimethylethyl ester2L [DAPT]) in the generation of cone and rod photoreceptors. Our results indicate that addition of RA + T3 during days 90 to 120 of differentiation enhanced the generation of rod and S-cone photoreceptor formation, while the combined addition of DAPT from days 28 to 42 with RA during days 30 to 120 of differentiation led to enhanced generation of L/M-cones at the expense of rods. l-DOPA when added together with RA during days 90 to 120 of differentiation also promoted the emergence of S-cones at the expense of rod photoreceptors. Collectively, these data represent an advance in our ability to direct generation of rod and cone photoreceptors in vitro.

Indexed as

Cell DifferentiationHumansOrganoidsPhotoreceptor Cells, VertebratePluripotent Stem CellsRetinaRetinal Cone Photoreceptor CellsRetinal Rod Photoreceptor Cellsphotoreceptorspluripotent stem cellsretinal organoids

Identifiers

PMID31670434
PMCPMC7004057
OpenAlexW2982588193

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.