Abstract
Corneal endothelial insufficiency is one of the leading causes of blindness. The main contemporary treatment for corneal blindness is endothelial keratoplasty, which, however, is unsatisfactory as a medical therapy due to the lack of donor corneas and graft rejection. Therefore, autologous stem cell-based corneal endothelial tissue substitutes may be a promising alternative to conventional grafts in the future. To address the age of most patients suffering from corneal endothelial deficiencies, we investigated the presence and potential of hair-derived stem cells from older tissue donors. Our studies revealed the presence of pluripotency- and neural crest-associated markers in tissue sections from blepharoplasty patients aged 50 to 80 years. In vitro outgrowths from eyelid hair follicles on collagen-coated tissue culture plates revealed a weak decrease in stem-cell potency. In contrast, cells within the spheres that spontaneously formed from the adherent cell layer retained full stem-cell potency and could be differentiated into cells of the ecto- meso and endodermal lineages. Although these highly potent hair follicle derived stem cells (HFSC) were only very slightly expandable, they were able to recognize the biomimicry of the Descemet’s-like topography and differentiate into corneal endothelial-like cells. In conclusion, HFSCs derived from epidermal skin of eyelid biopsies are a promising cell source to provide autologous corneal endothelial replacement for any age group of patients.Graphical
Highlights
The corneal endothelium covers the posterior surface of the cornea and is essential for clear vision as it maintains corneal hydration, thickness and transparency [1].Endothelial insufficiency may occur in cases of corneal injury or inherited or acquired endotheliopathies, postsurgical endothelial decompensation [2, 3], glaucoma-associated increased intraocular pressure [4, 5], pharmacologically induced edema [6], but can be caused by wearing contact lenses [7]
The co-localized expression of pluripotency transcription factor Oct-4 with Nestin an intermediate filament of stem or progenitor cells [23] as well as the expression of the gap junction protein Connexin-43 [24, 25] as a postulated marker for pre-migratory and migratory neural crest stem cells with the stage-specific embryonic antigen-4 (SSEA-4) a glycosphingolipid marker commonly known to be expressed in pluripotent cells which is downregulated through differentiation [26], supported the hypothesis of an immature stem cell population present in the hair follicle tissue region
CD133/1 is described as a marker of developmental hair follicle [29] and together with Lgr5, a marker for cycling and long-lived hair follicle stem cells [30], the present staining could indicate the existence of cycling hair follicles in aged eyelid skin samples
Summary
Endothelial insufficiency may occur in cases of corneal injury or inherited or acquired endotheliopathies, postsurgical endothelial decompensation [2, 3], glaucoma-associated increased intraocular pressure [4, 5], pharmacologically induced edema [6], but can be caused by wearing contact lenses [7]. This may result in corneal opacity or even blindness due to the insufficient regenerative capacity of the corneal endothelial tissue.
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