Human limbal epithelium contains side population cells expressing the ATP-binding cassette transporter ABCG2

WATANABE, K

doi:10.1016/s0014-5793(04)00358-8

Cited by 55 publications

(81 citation statements)

References 33 publications

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“…Although a surface marker for limbal epithelial stem cells has not been defined yet, several methods have been used to isolate stem cells from the limbal epithelium by FACS. Isolation of a side population based on Hoechst33342 dye exclusion that comprised less than 1% of all the cells has been reported by several groups (29,70,76,77,80,111,112). Sorting the side population revealed species specific differences.…”

Section: Isolation Of Lescmentioning

confidence: 93%

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Stem cells of the adult cornea: From cytometric markers to therapeutic applications

et al. 2008

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The cornea is a major protective shield of the interior of the eye and represents two thirds of its refractive power. It is made up of three tissue layers that have different developmental origins: the outer, epithelial layer develops from the ectoderm overlying the lens vesicle, whereas the stroma and the endothelium have mesenchymal origin. In the adult organism, the outermost corneal epithelium is the most exposed to environmental damage, and its constant renewal is assured by the epithelial stem cells that reside in the limbus, the circular border of the cornea. Cell turnover in the stromal layer is very slow and the endothelial cells probably do not reproduce in the adult organism. However, recent experimental evidence indicates that stem cells may be found in these layers. Damage to any of the corneal layers leads to loss of transparency and low vision. Corneal limbal stem cell deficiency results in severe ocular surface disease and its treatment by transplantating ex vivo expanded limbal epithelial cells is becoming widely accepted today. Stromal and endothelial stem cells are potential tools of tissue engineering and regenerative therapies of corneal ulcers and endothelial cell loss. In the past few years, intensive research has focused on corneal stem cells aiming to improve the outcomes of the current corneal stem cell transplantation techniques. This review summarizes the current state of knowledge on corneal epithelial, stromal and endothelial stem cells. Special emphasis is placed on the molecular markers that may help to identify these cells, and the recently revealed mechanisms that could maintain their ''stemness'' or drive their differentiation. The techniques for isolating and culturing/ expanding these cells are also described. '

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Section: Isolation Of Lescmentioning

confidence: 93%

“…Similarly to hematopoietic (69), skin and muscle cells, limbal epithelial cells also yield a stem cell rich side population (SP) when sorted after incubation with the Hoechst33342 dye (70,71). SP phenotype has been attributed to the function of the BCRP/ABCG2 transporter protein (72)(73)(74)(75).…”

Section: Abcg2mentioning

confidence: 99%

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

et al. 2008

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“…Using this method, SP cells have been isolated from human [23][24][25], rat [80], and rabbit [24,81,82] limbal tissues. The frequency of SP cells from the freshly isolated limbal epithelium varied from 0.2% to 0.64% in humans and from 0.4% to 1.21% in rabbits, while no SP cells were detected in human and rabbit central corneas.…”

Section: How Can Limbal Epithelial Scs and Their Niche Cells Be Isolamentioning

confidence: 99%

“…In contrast, the SC-containing limbal epithelium has a high proliferative potential in different cultures [12][13][14][15], and their in vitro proliferation is resistant to the inhibition by tumor-promoting phorbol esters [13,16,17]. Furthermore, limbal basal epithelial cells express cytokeratin 19 [18], and integrin a9 [10,19], and preferentially express such progenitor markers as p63 [20], especially its ∆Np63a isoform [21,22], Bcrp1/ABCG2 [10,[23][24][25], and N-cadherin [26].…”

Section: Introductionmentioning

confidence: 99%

Niche regulation of corneal epithelial stem cells at the limbus

et al. 2007

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Among all adult somatic stem cells, those of the corneal epithelium are unique in their exclusive location in a defined limbal structure termed Palisades of Vogt. As a result, surgical engraftment of limbal epithelial stem cells with or without ex vivo expansion has long been practiced to restore sights in patients inflicted with limbal stem cell deficiency. Nevertheless, compared to other stem cell examples, relatively little is known about the limbal niche, which is believed to play a pivotal role in regulating self-renewal and fate decision of limbal epithelial stem cells. This review summarizes relevant literature and formulates several key questions to guide future research into better understanding of the pathogenesis of limbal stem cell deficiency and further improvement of the tissue engineering of the corneal epithelium by focusing on the limbal niche.

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“…There was also very strong staining for LGR5, which has been suggested to be a marker for limbal stem cells in adult tissues (3). ABCG2 is expressed actively on the cellular surface, however cytoplasmic localisation is also possible (9). In order to confirm these observations gene expression was further investigated by PCR.…”

Section: Resultsmentioning

confidence: 95%

Molecular profile of organ culture-stored corneal epithelium: Lgr5 is a potential new phenotypic marker of residual human corneal limbal epithelial stem cells

et al. 2012

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Abstract. Long-term preservation of corneal limbal epithelium may decrease its quality and change the molecular signature of the limbal epithelial stem cells. In this study we have investigated the molecular profile of isolated corneal epithelial cells that have been in storage for an extended time. Isolated cells were characterised by the expression profile of different cytokeratins and markers of squamous metaplasia (vimentin and α-actin). Furthermore, we examined global markers of adult stem cells including p63α and ABCG2 but also LGR5 as a novel stem cell marker. Immunocytochemical staining and PCR analysis of p63α, ABCG2 and LGR5 revealed the existence of side-population cells with a stem-cell phenotype and maintenance of corneal limbal stem cell properties. LGR5 expression can be related to cellular stemness and can be considered as a new phenotypic marker of residual human corneal limbal stem cells. However, the existence of CK10 together with co-expressed α-actin and vimentin suggests that the corneas investigated were under oxidative stress and showed evidence of squamous metaplasia.

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Human limbal epithelium contains side population cells expressing the ATP-binding cassette transporter ABCG2

Cited by 55 publications

References 33 publications

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

Niche regulation of corneal epithelial stem cells at the limbus

Molecular profile of organ culture-stored corneal epithelium: Lgr5 is a potential new phenotypic marker of residual human corneal limbal epithelial stem cells

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