ArticlePloS one2013
Differentiation of human embryonic stem cells into cells with corneal keratocyte phenotype.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 76 citations in OpenAlex.
- Sphere-Derived Multipotent Progenitor Cells Obtained From Human Oral Mucosa Are Enriched in Neural Crest Cells.Stem cells translational medicine · 2016Trial
- Co-differentiation and enrichment of corneal endothelial cells and keratocytes from human pluripotent stem cells.Scientific reports · 2025Article
- Trehalose extricates impaired mitochondrial and autophagy dysregulation in patient iPSC-derived macular corneal dystrophy disease model.Stem cell research & therapy · 2024Article
- Embryoid body-based differentiation of human-induced pluripotent stem cells into cells with a corneal stromal keratocyte phenotype.BMJ open ophthalmology · 2024Article
- Directed Differentiation of Adipose-Derived Stem Cells Using Imprinted Cell-Like Topographies as a Growth Factor-Free Approach.Stem cell reviews and reports · 2024Review
- Mini review: human clinical studies of stem cell therapy in keratoconus.BMC ophthalmology · 2024Review
- Corneal stromal regeneration-keratoconus cell therapy: a review.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023Review
- Cell-based Therapies for Corneal and Retinal Disorders.Stem cell reviews and reports · 2023Review
- Assessment of the effects of intrastromal injection of adipose-derived stem cells in keratoconus patients.International journal of ophthalmology · 2023Article
- The Yin and Yang of Mesenchymal Cells in the Corneal Stromal Fibrosis Response to Injury: The Cornea as a Model of Fibrosis in Other Organs.Biomolecules · 2022Review
- Regenerative therapy for the Cornea.Progress in retinal and eye research · 2022Review
- Advances in Regulatory Strategies of Differentiating Stem Cells towards Keratocytes.Stem cells international · 2022Review
- Stem cell therapy in ocular pathologies in the past 20 years.World journal of stem cells · 2021Review
- Transcriptome dataset of human corneal endothelium based on ribosomal RNA-depleted RNA-Seq data.Scientific data · 2020Article
- Two-step induction of trabecular meshwork cells from induced pluripotent stem cells for glaucoma.Biochemical and biophysical research communications · 2020Article
- Fidelity of long-term cryopreserved adipose-derived stem cells for differentiation into cells of ocular and other lineages.Experimental eye research · 2019Article
- A Novel Human Pluripotent Stem Cell-Derived Neural Crest Model of Treacher Collins Syndrome Shows Defects in Cell Death and Migration.Stem cells and development · 2019Article
- Corneal cell therapy: with iPSCs, it is no more a far-sight.Stem cell research & therapy · 2018Review
- Postnatal periodontal ligament as a novel adult stem cell source for regenerative corneal cell therapy.Journal of cellular and molecular medicine · 2018Article
- Rs2459976 inOncotarget · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Corneal transparency depends on a unique extracellular matrix secreted by stromal keratocytes, mesenchymal cells of neural crest lineage. Derivation of keratocytes from human embryonic stem (hES) cells could elucidate the keratocyte developmental pathway and open a potential for cell-based therapy for corneal blindness. This study seeks to identify conditions inducing differentiation of pluripotent hES cells to the keratocyte lineage. Neural differentiation of hES cell line WA01(H1) was induced by co-culture with mouse PA6 fibroblasts. After 6 days of co-culture, hES cells expressing cell-surface NGFR protein (CD271, p75NTR) were isolated by immunoaffinity adsorption, and cultured as a monolayer for one week. Keratocyte phenotype was induced by substratum-independent pellet culture in serum-free medium containing ascorbate. Gene expression, examined by quantitative RT-PCR, found hES cells co-cultured with PA6 cells for 6 days to upregulate expression of neural crest genes including NGFR, SNAI1, NTRK3, SOX9, and MSX1. Isolated NGFR-expressing cells were free of PA6 feeder cells. After expansion as a monolayer, mRNAs typifying adult stromal stem cells were detected, including BMI1, KIT, NES, NOTCH1, and SIX2. When these cells were cultured as substratum-free pellets keratocyte markers AQP1, B3GNT7, PTDGS, and ALDH3A1 were upregulated. mRNA for keratocan (KERA), a cornea-specific proteoglycan, was upregulated more than 10,000 fold. Culture medium from pellets contained high molecular weight keratocan modified with keratan sulfate, a unique molecular component of corneal stroma. These results show hES cells can be induced to differentiate into keratocytes in vitro. Pluripotent stem cells, therefore, may provide a renewable source of material for development of treatment of corneal stromal opacities.
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Registered trials
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.