ArticleInvestigative ophthalmology & visual science2017
Mesenchymal Stem Cells Promote Diabetic Corneal Epithelial Wound Healing Through TSG-6-Dependent Stem Cell Activation and Macrophage Switch.
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. An erratum has been issued. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 120 citations in OpenAlex.
- TGF-BioMed research international · 2018Trial
- Abnormally low expression of tumor necrosis factor stimulated gene 6 (TSG-6) in obese type 2 diabetic mice contributes to altered inflammation and delayed cutaneous wound healing.bioRxiv : the preprint server for biology · 2026Article
- ROS-Responsive Eye Drop for Controlled Release of 20-Deoxyingenol Improves Diabetic Corneal Healing by Activating Macrophage Autophagy and Metabolic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- When Macrophages Heal and When They Scar: Timing in Corneal Fibrosis.Life (Basel, Switzerland) · 2026Review
- Macrophage metabolic reprogramming by vanadium released from glucose-responsive bio-gel accelerates diabetic wound repair.Signal transduction and targeted therapy · 2026Article
- Mechanistic Insights Into UC-MSC Therapy in a BAC-Induced Dry Eye Model: TSG-6-Dependent Inhibition of the Th17/CCL20-CCR6 Chemotactic Axis.Investigative ophthalmology & visual science · 2026Article
- Endogenous Therapeutic Agents for Acute Corneal and Ocular Surface Injuries.Translational vision science & technology · 2026Review
- Macrophage-Targeted Magnesium Ion-Nourisher for NLRP3 Inflammasome Inhibition to Enhance Liver Inflammatory Disease Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Diabetic keratopathy and nuclear proteins (Review).Molecular medicine reports · 2026Review
- Normal stress on surface of mesenchymal stem cells boosts extracellular vesicle secretion and regenerative bioactivity.Journal of nanobiotechnology · 2025Article
- The potential of exosomes in regenerative medicine and in the diagnosis and therapies of neurodegenerative diseases and cancer.Frontiers in medicine · 2025Review
- TSG-6 promotes healing of critical-sized bone defects in mice.Frontiers in immunology · 2025Article
- Advances in Stem Cell Therapy for Diabetic Foot Ulcers.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Effects of Bariatric Surgery-Related Weight Loss on the Characteristics, Metabolism, and Immunomodulation of Adipose Stromal/Stem Cells in a Follow-Up Study.Stem cells international · 2025Article
- Effect of Subconjunctival Injection of Canine Adipose-Derived Mesenchymal Stem Cells on Canine Spontaneous Corneal Epithelial Defects.Animals : an open access journal from MDPI · 2024Article
- The Role of Mesenchymal Stem Cells for Corneal Endothelial Regeneration: A Systematic Review.Rambam Maimonides medical journal · 2024Review
- The Role of Immune Cells and Signaling Pathways in Diabetic Eye Disease: A Comprehensive Review.Biomedicines · 2024Review
- Immune-Mediated Ocular Surface Disease in Diabetes Mellitus-Clinical Perspectives and Treatment: A Narrative Review.Biomedicines · 2024Review
- Role of mesenchymal stem cell-derived exosomes in the regeneration of different tissues.Journal of biological engineering · 2024Review
- Advanced multifunctional hydrogels for diabetic foot ulcer healing: Active substances and biological functions.Journal of diabetes · 2024Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: To explore the role and mechanism of bone marrow-derived mesenchymal stem cells (BM-MSCs) in corneal epithelial wound healing in type 1 diabetic mice. Methods: Diabetic mice were treated with subconjunctival injections of BM-MSCs or recombinant tumor necrosis factor-α-stimulated gene/protein-6 (TSG-6). The corneal epithelial wound healing rate was examined by fluorescein staining. The mRNA and protein expression levels of TSG-6 were measured by quantitative RT-PCR and Western blot. The infiltrations of leukocytes and macrophages were analyzed by flow cytometry and immunofluoresence staining. The effect of TSG-6 was further evaluated in cultured limbal epithelial stem/progenitor cells, macrophages, and diabetic mice by short hairpin RNA (shRNA) knockdown. Results: Local MSC transplantation significantly promoted diabetic corneal epithelial wound healing, accompanied by elevated corneal TSG-6 expression, increased corneal epithelial cell proliferation, and attenuated inflammatory response. Moreover, in cultured human limbal epithelial stem/progenitor cells, TSG-6 enhanced the colony-forming efficiency, stimulated mitogenic proliferation, and upregulated the expression level of ΔNp63. Furthermore, in diabetic mouse cornea and in vitro macrophage culture, TSG-6 alleviated leukocyte infiltration and promoted the polarization of recruited macrophages to anti-inflammatory M2 phenotypes with increased phagocytotic capacity. In addition, the promotion of epithelial stem/progenitor cell activation and macrophage polarization by MSC transplantation was largely abrogated by shRNA knockdown of TSG-6. Conclusions: This study provided the first evidence of TSG-6 secreted by MSCs promoting corneal epithelial wound healing in diabetic mice through activating corneal epithelial stem/progenitor cells and accelerating M2 macrophage polarization.
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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.