Cited by 486Retinal Development and DisordersPluripotent Stem Cells ResearchRetinal Diseases and Treatments

Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells

Open access
Idelson, Maria, Alper, Ruslana, Obolensky, Alexey, Ben-Shushan, Etti, Hemo, Itzhak, Yachimovich-Cohen, Nurit, Khaner, Hanita, Smith, Yoav +9 more·2009·Cell stem cell

Abstract

Dysfunction and loss of retinal pigment epithelium (RPE) leads to degeneration of photoreceptors in age-related macular degeneration and subtypes of retinitis pigmentosa. Human embryonic stem cells (hESCs) may serve as an unlimited source of RPE cells for transplantation in these blinding conditions. Here we show the directed differentiation of hESCs toward an RPE fate under defined culture conditions. We demonstrate that nicotinamide promotes the differentiation of hESCs to neural and subsequently to RPE fate. In the presence of nicotinamide, factors from the TGF-beta superfamily, which presumably pattern RPE development during embryogenesis, further direct RPE differentiation. The hESC-derived pigmented cells exhibit the morphology, marker expression, and function of authentic RPE and rescue retinal structure and function after transplantation to an animal model of retinal degeneration caused by RPE dysfunction. These results are an important step toward the future use of hESCs to replenish RPE in blinding diseases.

Integrity signals

Registry

Crossref · 10.1016/j.stem.2009.07.002

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Published protocols using directed approaches provide relatively efficient differentiation into cultures of cells reported to possess a wide range of RPE characteristics, including gene expression, polarized organization, and physiological and cell biological functions.

    “There are now published protocols using directed approaches that provide relatively efficient differentiation into cultures of cells, reported to possess a wide range of RPE characteristics, including gene expression, polarized organization, and physiological and cell biological functions (Idelson et al., 2009; Buchholz et al., 2013; Gong et al., 2015; Maruotti et al., 2015; Hazim et al., 2017).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Idelson et al., 2009

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Idelson, M., Alper, R., Obolensky, A., Ben-Shushan, E., Hemo, I., Yachimovich-Cohen, N., Khaner, H., Smith, Y., Wiser, O., Gropp, M., Cohen, M. A., Even-Ram, S., Berman-Zaken, Y., Matzrafi, L., Rechavi, G., Banin, E., & Reubinoff, B.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • Hadassah Medical Center (IL)
  • Sheba Medical Center (IL)
Corresponding author
Reubinoff, Benjamin
Venue
Cell stem cell
Publisher
Elsevier BV
Published
2009-10
Volume
5
Issue
4
Pages
396-408
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2092167465
Cited by
486
References
35
Citations by year
2026: 9 · 2025: 11 · 2024: 19 · 2023: 16 · 2022: 23 · 2021: 33 · 2020: 29 · 2019: 24 · 2018: 30 · 2017: 40 · 2016: 24 · 2015: 45 · 2014: 38 · 2013: 36 · 2012: 46
FWCI
14.56
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
Hebrew University of Jerusalem
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Keywords
retinal pigment epithelium, human embryonic stem cells, directed differentiation, nicotinamide, TGF-beta superfamily, neuronal differentiation, cell transplantation, retinal degeneration, age-related macular degeneration, retinitis pigmentosa, photoreceptor degeneration, stem cell therapy
MeSH terms
Animals, Cell Differentiation, Cell Line, Epithelial Cells, Flow Cytometry, Humans, Microscopy, Phase-Contrast, Immunophenotyping, Polymerase Chain Reaction, Transforming Growth Factor beta, Fibroblast Growth Factor 2, Cell Transplantation, Activins, Activin Receptors, Type I, Activin Receptors, Type II, Microscopy, Electron, Transmission, Rats, Embryonic Stem Cells, Retinal Pigment Epithelium

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review