Oligopotent stem cells are distributed throughout the mammalian ocular surface

Majo, F.; Rochat, Ariane; Nicolas, Michaël; Jaoudé, Georges Abou; Barrandon, Yann

doi:10.1038/nature07406

Cited by 382 publications

(376 citation statements)

References 31 publications

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“…This process does occur after extensive injury, but not in normal renewal in vivo [166]; in a number of species, cells right across the cornea are capable of forming holoclones expressing p63 and CK3. The limbus may be enriched in stem cells, and in man a SP based on ABCG2 activity has been identified that appeared to be highly clonogenic in vitro; these cells also expressed high levels of p63 and the α9 integrin [167,168].…”

Section: Eyementioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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Section: Eyementioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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“…23,24 By contrast, the stroma in the corneal deficiency model was vascularized (Figures 2b and c, asterisks), and the collagen fibrils were randomly oriented (Figure 2a-c), as has also been observed in the pannus of human SJS patients. 25 The 4-week corneal deficiency model surface showed expression of cytokeratin 13 (K13; Figure 2d), a conjunctival epithelial marker, 26,27 , and mucin 5AC (Muc5; Figure 2g), a goblet cell marker. Moreover, K12, a corneal epithelial cell marker, was absent from the 4-week corneal deficiency model surface ( Figure 2j).…”

Section: Condition Of the Ocular Surfaces And Epithelial Cell Phenotypementioning

confidence: 99%

Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up

Kameishi

Sugiyama

Yamato

et al. 2015

Laboratory Investigation

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The ocular surface consists of the cornea, conjunctiva, and the limbus that is located in the transitional zone between the cornea and conjunctiva. The corneal epithelial cells are generated through the mitosis of corneal epithelial stem cells in the limbus. This study investigated a rabbit corneal deficiency model prepared by the surgical removal of the corneal and limbal epithelia, which express cytokeratin 12 (K12). After the surgery, K13-expressing conjunctival epithelium migrated onto the corneal surface and completely covered the surface, leading to neovascularization and corneal opacification. However, at 24 and 48 weeks after the surgery, K12-expressing cornea-like cells reappeared on the model ocular surface. These cells formed an island surrounded by invaded conjunctiva and were isolated from the limbus. Interestingly, in the 24-week model surface, a1(IV) and a2(IV) collagen chains, which are normally found in the basement membrane of the native limbus and conjunctiva, and not in the cornea, were continuously deposited throughout the entire basement membrane, including the basement membrane under cornea-like cells. By contrast, in the 48-week model surface, a1(IV) and a2(IV) collagen chains were absent from the basement membrane beneath the central part of cornea-like cells and were localized below the invaded conjunctiva and the transitional zone between cornea-like cells and the invaded conjunctiva, which had similar distribution to the native ocular basement membrane. Moreover, K12, K14, p63, vimentin, and a1(IV) and a2(IV) collagen chains, which are colocalized in the native limbus, were all present at the transitional zone of the 48-week model surface. Therefore, a limbus-like structure appeared to be reconstructed on the surface of the 48-week model as a stem cell niche. This study should aid in the understanding of human corneal deficiency, the correlation between the epithelial cell phenotype and the composition of the basement membrane, and the epithelial stem cell niche.

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“…The dogma that stem cells of the cornea reside solely in the limbus has been challenged by Majo et al (2008). In their controversial paper, they showed that the central cornea of the mouse contains oligopotent stem cells [5].…”

Section: Challenges and Controversiesmentioning

confidence: 99%

Concise Review: Limbal Epithelial Stem Cell Therapy: Controversies and Challenges

O’Callaghan

Daniels

2011

Stem Cells

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Limbal epithelial stem cells (LESCs) are a population of stem cells responsible for maintenance and repair of the corneal surface. Injury and disease can result in a deficiency of these stem cells, the vision affecting condition called limbal stem cell deficiency (LSCD) in which the cornea becomes opaque, vascularized, and inflamed. Cultured LESC therapy was first described in 1997, and LESCs cultured from either patients or donors have been used to successfully treat LSCD. In this review, some of the challenges and controversies associated with cultured LESC therapy will be discussed including alternative stem cell sources.

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Oligopotent stem cells are distributed throughout the mammalian ocular surface

Cited by 382 publications

References 31 publications

Attributes of adult stem cells

Attributes of adult stem cells

Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up

Concise Review: Limbal Epithelial Stem Cell Therapy: Controversies and Challenges

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