Evidence map›Paper›PMID 25069777›Full record

ArticleStem cells translational medicine2014

Differentiation of human limbal-derived induced pluripotent stem cells into limbal-like epithelium.

Dhruv Sareen, Mehrnoosh Saghizadeh, Loren Ornelas, Michael A Winkler, Kavita Narwani, Anais Sahabian, Vincent A Funari, Jie Tang, Lindsay Spurka, Vasu Punj and 4 more

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

Article in Stem cells translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
10.2field-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

51 citing papers in PubMed, 84 citations in OpenAlex.

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  12. Genetic disruption of zebrafish mab21l1 reveals a conserved role in eye development and affected pathways.Developmental dynamics : an official publication of the American Association of Anatomists · 2021
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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

14 authors at 3 institutions in 1 country.

Dhruv SareenRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Mehrnoosh SaghizadehRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Loren OrnelasRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Michael A WinklerRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Kavita NarwaniRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Anais SahabianRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Vincent A FunariRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Jie TangRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Lindsay SpurkaRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Vasu PunjRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Ezra MaguenRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Yaron S RabinowitzRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Clive N SvendsenRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Alexander V LjubimovRegenerative Medicine Institute, Eye Program, and Departments of Biomedical Sciences, Neurosurgery, Genomics Core, and Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Norris Comprehensive Cancer Center Bioinformatics Core and Division of Hematology, University of Southern California, Los Angeles, California, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA ljubimov@cshs.org.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · USUniversity of Southern California · US

Funding

Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Mechanisms of Epithelial Alterations in Diabetic CorneaR01EY013431 · NEI · CEDARS-SINAI MEDICAL CENTER · PI Alexander V Ljubimov · 2001 to 2026
$11.3M
Transplantable limbal cells from induced pluripotent stem cellsR01EY023429 · NEI · CEDARS-SINAI MEDICAL CENTER · PI LJUBIMOV, ALEXANDER V · 2013 to 2015
$1.2M
The Role and Mechanisms of microRNAs in Diabetic CorneaR21EY022771 · NEI · CEDARS-SINAI MEDICAL CENTER · PI GHIAM, MEHRNOOSH SAGHIZADEH · 2012 to 2013
$443k
NEI NIH HHS EY013431NEI NIH HHS EY023429NEI NIH HHS R01 EY013431NEI NIH HHS R01 EY023429NEI NIH HHS R21 EY022771
6 · The paper itself

Abstract

Limbal epithelial stem cell (LESC) deficiency (LSCD) leads to corneal abnormalities resulting in compromised vision and blindness. LSCD can be potentially treated by transplantation of appropriate cells, which should be easily expandable and bankable. Induced pluripotent stem cells (iPSCs) are a promising source of transplantable LESCs. The purpose of this study was to generate human iPSCs and direct them to limbal differentiation by maintaining them on natural substrata mimicking the native LESC niche, including feederless denuded human amniotic membrane (HAM) and de-epithelialized corneas. These iPSCs were generated with nonintegrating vectors from human primary limbal epithelial cells. This choice of parent cells was supposed to enhance limbal cell differentiation from iPSCs by partial retention of parental epigenetic signatures in iPSCs. When the gene methylation patterns were compared in iPSCs to parental LESCs using Illumina global methylation arrays, limbal-derived iPSCs had fewer unique methylation changes than fibroblast-derived iPSCs, suggesting retention of epigenetic memory during reprogramming. Limbal iPSCs cultured for 2 weeks on HAM developed markedly higher expression of putative LESC markers ABCG2, ΔNp63α, keratins 14, 15, and 17, N-cadherin, and TrkA than did fibroblast iPSCs. On HAM culture, the methylation profiles of select limbal iPSC genes (including NTRK1, coding for TrkA protein) became closer to the parental cells, but fibroblast iPSCs remained closer to parental fibroblasts. On denuded air-lifted corneas, limbal iPSCs even upregulated differentiated corneal keratins 3 and 12. These data emphasize the importance of the natural niche and limbal tissue of origin in generating iPSCs as a LESC source with translational potential for LSCD treatment.

Indexed as

Cell Culture TechniquesCell DifferentiationEpithelium, CornealHumansImmunohistochemistryInduced Pluripotent Stem CellsLimbus CorneaeOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionAmniotic membraneiPS cellLimbal epitheliumLimbal stem cell deficiencyMethylationTrkA

Identifiers

PMID25069777
PMCPMC4149305
OpenAlexW2100601473

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.