Evidence map›Paper›PMID 28969679›Full record

ArticleStem cell research & therapy2017

Differentiation of RPE cells from integration-free iPS cells and their cell biological characterization.

Roni A Hazim, Saravanan Karumbayaram, Mei Jiang, Anupama Dimashkie, Vanda S Lopes, Douran Li, Barry L Burgess, Preethi Vijayaraj, Jackelyn A Alva-Ornelas, Jerome A Zack and 5 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

41 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Atrophic Macular Degeneration and Stem Cell Therapy: A Clinical Review.Advances in experimental medicine and biology · 2025
    Review
  6. Review
  7. Article
  8. Molecular and cellular imaging of the eye.Biomedical optics express · 2024
    Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 1 country.

Roni A HazimStein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, 100 Stein Plaza, Los Angeles, CA, 90095, USA.
Saravanan KarumbayaramDepartment of Microbiology Immunology and Molecular Genetics, Los Angeles, CA, USA. Skarumbayaram@mednet.ucla.edu.
Mei JiangStein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, 100 Stein Plaza, Los Angeles, CA, 90095, USA.
Anupama DimashkieEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, Los Angeles, CA, USA.
Vanda S LopesStein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, 100 Stein Plaza, Los Angeles, CA, 90095, USA.
Douran LiStein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, 100 Stein Plaza, Los Angeles, CA, 90095, USA.
Barry L BurgessStein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, 100 Stein Plaza, Los Angeles, CA, 90095, USA.
Preethi VijayarajDepartment of Pediatrics, David Geffen School of Medicine, Los Angeles, CA, USA.
Jackelyn A Alva-OrnelasDepartment of Population Sciences, City of Hope National Medical Center, Duarte, CA, USA.
Jerome A ZackDepartment of Microbiology Immunology and Molecular Genetics, Los Angeles, CA, USA.
Donald B KohnDepartment of Microbiology Immunology and Molecular Genetics, Los Angeles, CA, USA.
Brigitte N GompertsDepartment of Pediatrics, David Geffen School of Medicine, Los Angeles, CA, USA.
April D PyleDepartment of Microbiology Immunology and Molecular Genetics, Los Angeles, CA, USA.
William E LowryDepartment of Molecular Cell and Developmental Biology, Los Angeles, CA, USA.
David S WilliamsStein Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, 100 Stein Plaza, Los Angeles, CA, 90095, USA. dswilliams@ucla.edu.
Broad Center · USUCLA Jonsson Comprehensive Cancer CenterUniversity of California, Los Angeles · USUniversity of Colorado Denver · USCity Of Hope National Medical Center · US

Funding

Vision Research Core at UCLAP30EY000331 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Xian-Jie Yang · 1985 to 2026
$16.8M
Reprogramming and Directed Differentiation of Skeletal Muscle Cells from hPSCs.R01AR064327 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI April D Pyle · 2013 to 2026
$6.4M
UCLA Muscular Dystrophy Core CenterP30AR057230 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MICELI, M CARRIE · 2009 to 2018
$6.2M
The Photoreceptor CiliumR01EY013408 · NEI · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI WILLIAMS, DAVID S · 2001 to 2017
$3.8M
RPE cell biology, aging, and diseaseR01EY027442 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WILLIAMS, DAVID S · 2017 to 2021
$2.6M
CFH in RPE cell biology and diseaseF31EY026805 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HAZIM, RONI · 2017 to 2018
$65k
NEI NIH HHS F31 EY026805NEI NIH HHS P30 EY000331NEI NIH HHS R01 EY013408NEI NIH HHS R01 EY027442NIAMS NIH HHS P30 AR057230NIAMS NIH HHS R01 AR064327
6 · The paper itself

Abstract

backgroundDysfunction of the retinal pigment epithelium (RPE) is implicated in numerous forms of retinal degeneration. The readily accessible environment of the eye makes it particularly suitable for the transplantation of RPE cells, which can now be derived from autologous induced pluripotent stem cells (iPSCs), to treat retinal degeneration. For RPE transplantation to become feasible in the clinic, patient-specific somatic cells should be reprogrammed to iPSCs without the introduction of reprogramming genes into the genome of the host cell, and then subsequently differentiated into RPE cells that are well characterized for safety and functionality prior to transplantation.

methodsWe have reprogrammed human dermal fibroblasts to iPSCs using nonintegrating RNA, and differentiated the iPSCs toward an RPE fate (iPSC-RPE), under Good Manufacturing Practice (GMP)-compatible conditions.

resultsUsing highly sensitive assays for cell polarity, structure, organelle trafficking, and function, we found that iPSC-RPE cells in culture exhibited key characteristics of native RPE. Importantly, we demonstrate for the first time with any stem cell-derived RPE cell that live cells are able to support dynamic organelle transport. This highly sensitive test is critical for RPE cells intended for transplantation, since defects in intracellular motility have been shown to promote RPE pathogenesis akin to that found in macular degeneration. To test their capabilities for in-vivo transplantation, we injected the iPSC-RPE cells into the subretinal space of a mouse model of retinal degeneration, and demonstrated that the transplanted cells are capable of rescuing lost RPE function.

conclusionsThis report documents the successful generation, under GMP-compatible conditions, of human iPSC-RPE cells that possess specific characteristics of healthy RPE. The report adds to a growing literature on the utility of human iPSC-RPE cells for cell culture investigations on pathogenicity and for therapeutic transplantation, by corroborating findings of others, and providing important new information on essential RPE cell biological properties.

Indexed as

AnimalsCell DifferentiationCell PolarityCellular ReprogrammingDisease Models, AnimalEncephalitis Virus, Venezuelan EquineEpithelial CellsFibroblastsGenetic VectorsHumansInduced Pluripotent Stem CellsInjections, IntraocularIntercellular Signaling Peptides and ProteinsMiceMice, Inbred BALB CMice, KnockoutIntercellular Signaling Peptides and ProteinsInduced pluripotent stem cellsLive-cell imagingPhagocytosisRetinal pigment epitheliumRPE cytoskeleton

Identifiers

PMID28969679
PMCPMC5625837
OpenAlexW2764102165

What OpenQuestion 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 OpenQuestion graph.