Evidence map›Paper›PMID 23833067›Full record

ArticleInvestigative ophthalmology & visual science2013

Subretinal implantation of retinal pigment epithelial cells derived from human embryonic stem cells: improved survival when implanted as a monolayer.

Bruno Diniz, Padmaja Thomas, Biju Thomas, Ramiro Ribeiro, Yuntao Hu, Rodrigo Brant, Ashish Ahuja, Danhong Zhu, Laura Liu, Michael Koss and 4 more

Open access · hybridAbstract readComparative Study
In one paragraph

Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 2 pooled it
9.1field-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

119 citing papers in PubMed, 2 syntheses or guidelines pooled it, 241 citations in OpenAlex.

  1. Pooled it
  2. [Stem cell therapy for retinal diseases].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2015
    Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Cell therapy for age-related macular degeneration.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Animal models for the evaluation of retinal stem cell therapies.Progress in retinal and eye research · 2025
    Review
  15. Atrophic Macular Degeneration and Stem Cell Therapy: A Clinical Review.Advances in experimental medicine and biology · 2025
    Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

59 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

14 authors at 5 institutions in 5 countries.

Bruno DinizDoheny Eye Institute, Los Angeles, California, USA. dinizb@me.com
Padmaja Thomas
Biju Thomas
Ramiro Ribeiro
Yuntao Hu
Rodrigo Brant
Ashish Ahuja
Danhong Zhu
Laura Liu
Michael Koss
Mauricio Maia
Gerald Chader
David R Hinton
Mark S Humayun
Doheny Eye Institute · USUniversity of Southern California · USUniversidade Federal de São Paulo · BRGoethe University Frankfurt · DEPeking University · CN

Funding

VISION RESEARCHP30EY003040 · NEI · DOHENY EYE INSTITUTE · PI SUN, DEMING · 1985 to 2013
$7.0M
NEI NIH HHS EY03040NEI NIH HHS P30 EY003040
6 · The paper itself

Abstract

purposeTo evaluate cell survival and tumorigenicity of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM).

methodsSixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker).

resultsThe implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group.

conclusionshESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects.

Indexed as

AnimalsCell DifferentiationCells, CulturedCell SurvivalDisease Models, AnimalEmbryonic Stem CellsEpithelial CellsEye ProteinsFemaleHumansMacular DegenerationMaleRatsRats, NudeRetinaRetinal Pigment EpitheliumEye Proteinsage-related macular degenerationhuman embryonic stem cellsretinal pigment epithelium

Identifiers

PMID23833067
PMCPMC3726243
OpenAlexW2062460463

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.