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Tissue-Specific Stem Cells
Article first published online: 2 MAR 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 3, pages 642–652, March 2009
How to Cite
Blazejewska, E. A., Schlötzer-Schrehardt, U., Zenkel, M., Bachmann, B., Chankiewitz, E., Jacobi, C. and Kruse, F. E. (2009), Corneal Limbal Microenvironment Can Induce Transdifferentiation of Hair Follicle Stem Cells into Corneal Epithelial-like Cells. STEM CELLS, 27: 642–652. doi: 10.1634/stemcells.2008-0721
Author contributions: E.A.B.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; U.S.-S.: conception and design, data analysis and interpretation, manuscript writing; M.Z.: conception and design, data analysis and interpretation; B.B.: conception and design, data analysis and interpretation; E.C.: conception and design, data analysis and interpretation; C.J.: conception and design, data analysis and interpretation; F.E.K.: conception and design, data analysis and interpretation, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSExpress December 11, 2008; available online without subscription through the open access option.
- Issue published online: 2 MAR 2009
- Article first published online: 2 MAR 2009
- Manuscript Accepted: 15 NOV 2008
- Manuscript Received: 29 JUL 2008
- Adult stem cells;
- Hair follicle;
- Epithelial lineages;
- Limbal stem cell niche
The aim of this study was to investigate the transdifferentiation potential of murine vibrissa hair follicle (HF) stem cells into corneal epithelial-like cells through modulation by corneal- or limbus-specific microenvironmental factors. Adult epithelial stem cells were isolated from the HF bulge region by mechanical dissection or fluorescence-activated cell sorting using antibodies to α6 integrin, enriched by clonal expansion, and subcultivated on various extracellular matrices (type IV collagen, laminin-1, laminin-5, fibronectin) and in different conditioned media derived from central and peripheral corneal fibroblasts, limbal stromal fibroblasts, and 3T3 fibroblasts. Cellular phenotype and differentiation were evaluated by light and electron microscopy, real-time reverse transcription-polymerase chain reaction, immunocytochemistry, and Western blotting, using antibodies against putative stem cell markers (K15, α6 integrin) and differentiation markers characteristic for corneal epithelium (K12, Pax6) or epidermis (K10). Using laminin-5, a major component of the corneo-limbal basement membrane zone, and conditioned medium from limbal stromal fibroblasts, clonally enriched HF stem and progenitor cells adhered rapidly and formed regularly arranged stratified cell sheets. Conditioned medium derived from limbal fibroblasts markedly upregulated expression of cornea-specific K12 and Pax6 on the mRNA and protein level, whereas expression of the epidermal keratinocyte marker K10 was strongly downregulated. These findings suggest that adult HF epithelial stem cells are capable of differentiating into corneal epithelial-like cells in vitro when exposed to a limbus-specific microenvironment. Therefore, the HF may be an easily accessible alternative therapeutic source of autologous adult stem cells for replacement of the corneal epithelium and restoration of visual function in patients with ocular surface disorders. STEM CELLS2009;27:642–652