Evidence map›Paper›PMID 26283078›Full record

ArticleStem cells and development2015

Characterization of Three-Dimensional Retinal Tissue Derived from Human Embryonic Stem Cells in Adherent Monolayer Cultures.

Ratnesh K Singh, Ramya K Mallela, Pamela K Cornuet, Aaron N Reifler, Andrew P Chervenak, Michael D West, Kwoon Y Wong, Igor O Nasonkin

Open access · greenAbstract read
In one paragraph

Article in Stem cells and development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

37 citing papers in PubMed, 56 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Toward Retinal Organoids in High-Throughput.Cold Spring Harbor perspectives in medicine · 2024
    Review
  5. Review
  6. Article
  7. Article
  8. Re-formation of synaptic connectivity in dissociated human stem cell-derived retinal organoid cultures.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. Review
  10. Review
  11. Retinal Organoids and Retinal Prostheses: An Overview.International journal of molecular sciences · 2022
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Pluripotent Stem Cell-Based Organoid Technologies for Developing Next-Generation Vision Restoration Therapies of Blindness.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2021
    Review
  18. NRLStem cells (Dayton, Ohio) · 2021
    Article
  19. Article
  20. Article
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 1 institution in 1 country.

Ratnesh K Singh1 Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
Ramya K Mallela1 Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
Pamela K Cornuet1 Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
Aaron N Reifler2 Department of Ophthalmology and Visual Sciences, University of Michigan , Ann Arbor, Michigan.
Andrew P Chervenak2 Department of Ophthalmology and Visual Sciences, University of Michigan , Ann Arbor, Michigan.
Michael D West3 BioTime, Inc. , Alameda, California.
Kwoon Y Wong2 Department of Ophthalmology and Visual Sciences, University of Michigan , Ann Arbor, Michigan.
Igor O Nasonkin1 Department of Ophthalmology, Louis J. Fox Center for Vision Restoration, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
University of Michigan–Ann Arbor · US

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
VIVARIUM MODULEP30EY007003 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Antonetti · 1987 to 2026
$17.6M
NEI NIH HHS P30 EY007003NEI NIH HHS P30 EY008098
6 · The paper itself

Abstract

Stem cell-based therapy of retinal degenerative conditions is a promising modality to treat blindness, but requires new strategies to improve the number of functionally integrating cells. Grafting semidifferentiated retinal tissue rather than progenitors allows preservation of tissue structure and connectivity in retinal grafts, mandatory for vision restoration. Using human embryonic stem cells (hESCs), we derived retinal tissue growing in adherent conditions consisting of conjoined neural retina and retinal pigment epithelial (RPE) cells and evaluated cell fate determination and maturation in this tissue. We found that deriving such tissue in adherent conditions robustly induces all eye field genes (RX, PAX6, LHX2, SIX3, SIX6) and produces four layers of pure populations of retinal cells: RPE (expressing NHERF1, EZRIN, RPE65, DCT, TYR, TYRP, MITF, PMEL), early photoreceptors (PRs) (coexpressing CRX and RCVRN), inner nuclear layer neurons (expressing CALB2), and retinal ganglion cells [RGCs, expressing BRN3B and Neurofilament (NF) 200]. Furthermore, we found that retinal progenitors divide at the apical side of the hESC-derived retinal tissue (next to the RPE layer) and then migrate toward the basal side, similar to that found during embryonic retinogenesis. We detected synaptogenesis in hESC-derived retinal tissue, and found neurons containing many synaptophysin-positive boutons within the RGC and PR layers. We also observed long NF200-positive axons projected by RGCs toward the apical side. Whole-cell recordings demonstrated that putative amacrine and/or ganglion cells exhibited electrophysiological responses reminiscent of those in normal retinal neurons. These responses included voltage-gated Na(+) and K(+) currents, depolarization-induced spiking, and responses to neurotransmitter receptor agonists. Differentiation in adherent conditions allows generation of long and flexible pieces of 3D retinal tissue suitable for isolating transplantable slices of tissue for retinal replacement therapies.

Indexed as

Tissue EngineeringAction PotentialsCells, CulturedEmbryonic Stem CellsHumansNeurogenesisPotassiumRetinal NeuronsRetinal Pigment EpitheliumSodiumSynapsesSynaptophysinPotassiumSodiumSynaptophysin

Identifiers

PMID26283078
PMCPMC4653822
OpenAlexW2104853825

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.