ArticleInvestigative ophthalmology & visual science2017
Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
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.
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Who cites it
52 citing papers in PubMed, 77 citations in OpenAlex.
- 2-kDa hyaluronan ameliorates human facial wrinkles through increased dermal collagen density related to promotion of collagen remodeling.Journal of cosmetic dermatology · 2023Trial
- Ocular Surface Inflammation as a Driver of Cornea Limbal Stem Cell Deficiency: Mechanisms and Implications.International journal of molecular sciences · 2026Review
- Applied Anatomical and Morphological Characterization of the Ocular Surface of the African Spiny Mice: Acomys cahirinus.Investigative ophthalmology & visual science · 2026Article
- Limbal Epithelial Stem Cells in Review: Immune and Lymphangiogenic Privilege and Their Clinical Relevance.Cells · 2026Review
- In Vivo Evaluation of Injected and Bioprinted Hyaluronic Acid-Based Bioink in Corneal Stromal Pocket.Macromolecular bioscience · 2026Article
- Engineered Tandem Thymosin Peptide Promotes Corneal Wound Healing.Investigative ophthalmology & visual science · 2025Article
- Article
- Comparative Analysis of Age-Associated Changes in Meibum Composition, Distribution, and Function in Mice With Altered Hyaluronan Expression.Investigative ophthalmology & visual science · 2025Article
- Correlation of Multimodal Clinical Imaging With the Whole-Slide- and Superresolution-Based Immunohistological Structure of the Corneal Limbal Stroma.Investigative ophthalmology & visual science · 2025Article
- Low fucosylation defines the glycocalyx of progenitor cells and melanocytes in the human limbal stem cell niche.Stem cell reports · 2025Article
- The impact of the limbal niche interactions on the self-renewal capability of limbal epithelial stem cells.Frontiers in cell and developmental biology · 2025Article
- Development of Biomimetic Substrates for Limbal Epithelial Stem Cells Using Collagen-Based Films, Hyaluronic Acid, Immortalized Cells, and Macromolecular Crowding.Life (Basel, Switzerland) · 2024Article
- Hyaluronate Protects From Benzalkonium Chloride-Induced Ocular Surface Toxicity.Translational vision science & technology · 2024Article
- Biomimetic Hyaluronan Binding Biomaterials to Capture the Complex Regulation of Hyaluronan in Tissue Development and Function.Biomimetics (Basel, Switzerland) · 2024Review
- Review
- Endogenous TSG-6 modulates corneal inflammation following chemical injury.The ocular surface · 2024Article
- Eyes open on stem cells.Stem cell reports · 2023Review
- Age related changes in hyaluronan expression leads to Meibomian gland dysfunction.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Characterization of the Limbal Epithelial Stem Cell Niche.Investigative ophthalmology & visual science · 2023Article
- ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing.Biomolecules · 2023Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Purpose: Limbal epithelial stem cells (LSCs), located in the basal layer of the corneal epithelium in the corneal limbus, are vital for maintaining the corneal epithelium. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. To date, limited research has focused on unveiling the composition of the limbal stem cell niche, and, more important, on the role the specific stem cell niche may have in LSC differentiation and function. Our work investigates the composition of the extracellular matrix in the LSC niche and how it regulates LSC differentiation and function. Methods: Hyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice-HAS1-/-;HAS3-/-, HAS2Δ/ΔCorEpi, TSG-6-/--were used to determine the importance of the HA niche in LSC differentiation and specification. Results: Our data demonstrate that the LSC niche is composed of a HA rich extracellular matrix. HAS1-/-;HAS3-/-, HAS2Δ/ΔCorEpi, and TSG-6-/- mice have delayed wound healing and increased inflammation after injury. Interestingly, upon insult the HAS knock-out mice up-regulate HA throughout the cornea through a compensatory mechanism, and in turn this alters LSC and epithelial cell specification. Conclusions: The LSC niche is composed of a specialized HA matrix that differs from that present in the rest of the corneal epithelium, and the disruption of this specific HA matrix within the LSC niche leads to compromised corneal epithelial regeneration. Finally, our findings suggest that HA has a major role in maintaining the LSC phenotype.
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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.