The Role of Limbal Stem Cells in Corneal Epithelial Maintenance

Dua, Harminder S.; Miri, Ammar; Alomar, Thaer; Yeung, Aaron M.; Said, Dalia G.

doi:10.1016/j.ophtha.2008.12.017

Cited by 122 publications

(112 citation statements)

References 26 publications

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“…Similarly, the mouse corneal epithelium was able to sustain itself for four months after the limbus was cauterised to destroy the limbal epithelium [1] . It has also been reported that some patients with symptoms of total LESC deficiency retain central islands of normal corneal epithelium for several years [41] and in one case this appeared to be sufficient to restore the corneal epithelium [42] . These studies show that the central cornea can maintain itself to some extent when the limbus is eliminated or disconnected.…”

Section: Cells With High Proliferative Potentialmentioning

confidence: 88%

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

West¹,

Dora²,

Collinson

2015

WJSC

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In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell (LESC) hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient (or transit) amplifying cells (TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell (CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis.

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Section: Cells With High Proliferative Potentialmentioning

confidence: 88%

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

West¹,

Dora²,

Collinson

2015

WJSC

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“…Some patients who had 360° LSCD were found to have normal corneas for up to 12 years [121] . Also in LSCD patients who received ex vivo expanded limbal cell transplants, donor limbal cells that only lasted for 28 wk [122] or 9 mo [123] still resulted in the long-term restoration of the central corneal epithelium.…”

Section: Limbus-independent Corneal Maintenancementioning

confidence: 99%

“…Assuming desquamation of superficial cell layer occurs constantly, there are a few possible scenarios; (1) the amount of limbal stem cells remaining is undetectable but just enough to maintain homeostasis; (2) TACs in the basal cell layer of the central epithelium have an unexpected life span and a greater than previously thought proliferative potential; or (3) a self-renewing pool of precursor cells exist in the central cornea. Two independent groups have proposed the existence of a conceptual type of cell in the central corneal epithelium which is a TAC with more stem cell-like characteristics [121,124] . Further research efforts are required to explore and clarify these possibilities although a TAC cell with more stem cell-like characteristics sounds uncommonly similar to a stem cell.…”

Section: Limbus-independent Corneal Maintenancementioning

confidence: 99%

Limbal stem cells: Central concepts of corneal epithelial homeostasis

Yoon¹

2014

WJSC

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A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent studies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal surface

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“…However, their human data did not appear to support this theory [6] suggesting that there may be species-specific differences in the location of corneal stem cells. Although it is widely accepted that stem cells of the cornea reside in the limbus, several other studies have suggested that this is not the only location of cells which can regenerate the corneal epithelium [7,8]. A study by Dua et al (2009) looked at eight eyes all of which had a central area of normal corneal epithelium despite being LESC deficient.…”

Section: Challenges and Controversiesmentioning

confidence: 99%

“…Although it is widely accepted that stem cells of the cornea reside in the limbus, several other studies have suggested that this is not the only location of cells which can regenerate the corneal epithelium [7,8]. A study by Dua et al (2009) looked at eight eyes all of which had a central area of normal corneal epithelium despite being LESC deficient. These normal areas remained unchanged over a mean follow-up of 60 months.…”

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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The Role of Limbal Stem Cells in Corneal Epithelial Maintenance

Cited by 122 publications

References 26 publications

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

Limbal stem cells: Central concepts of corneal epithelial homeostasis

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

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