Differences in sphere-forming cells from keratoconic and normal corneal tissue: Implications for keratoconus pathogenesis
| Autor: | Bert van der Werf, Ye Li, Trevor Sherwin, Salim Ismail, Jennifer J. McGhee, Nikita Noord, Himanshu Wadhwa |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Keratoconus Pathology medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Stromal cell genetic structures Biology Stem cell marker Polymerase Chain Reaction Cornea 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Proliferating Cell Nuclear Antigen Spheroids Cellular medicine Humans Receptor Notch1 Progenitor cell Cells Cultured Wound Healing medicine.disease Immunohistochemistry Actins Tissue Donors eye diseases Sensory Systems Corneal Disorder Ophthalmology 030104 developmental biology 030221 ophthalmology & optometry sense organs Stem cell Wound healing Myofibroblast Biomarkers |
| Zdroj: | Experimental Eye Research. 202:108301 |
| ISSN: | 0014-4835 |
| Popis: | Keratoconus is primarily an anterior corneal disorder of unclear aetiology. Stem cells may play a role in the perpetuation of keratoconus, although this has yet to be definitively established. Sphere-forming cells from normal human donor corneas have previously been shown to be a heterogenous mix of epithelial, stromal, stem and progenitor cell components which have potential for treatment of corneal dystrophies. Our work set out to isolate and characterise sphere-forming cells from human keratoconic tissue. Keratoconic donor corneas were successfully used to culture sphere-forming cells in vitro. Time lapse imaging of these spheres on a collagen surface over 8 days revealed keratoconic spheres lack the ability to maintain a central core and have diminished ability to repopulate the surface. Immunocytochemistry showed positive labelling for the stem cell marker 'Adenosine triphosphate-binding cassette sub-family B member 5 (ABCB5)' indicating stem cell retention and the myofibroblast marker alpha smooth muscle actin indicating wound repair while droplet digital Polymerase Chain Reaction confirmed an increase in expression of stem and stromal cell markers in keratoconic spheres compared to spheres cultured from normal donors at day 7 post-placement. Keratoconic sphere-forming cells showed a diminished repopulation ability, a faster wound healing response and lack of central core retention. These results suggest stem cells in keratoconus may be in an elevated state of wound repair and unable to respond appropriately to further injury in corneal maintenance. Sphere forming cell populations in keratoconus appear to be different to those isolated from normal corneas and this may be an important consideration in unearthing keratoconus aetiology. |
| Databáze: | OpenAIRE |
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