Existence of small slow-cycling Langerhans cells in the limbal basal epithelium that express ABCG2

Chen, Wensheng; Hara, Koji; Tian, Qinghua; Zhao, Kan-xing; Yoshitomi, Takeshi

doi:10.1016/j.exer.2006.11.006

Cited by 50 publications

(48 citation statements)

References 29 publications

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“…The presumption that the dendritic cells observed with CCM are Langerhans cells and not another subset of dendritic cells is supported by previous findings that Langerhans cell‐specific surface markers are expressed by dendritic cells in the corneal and limbal epithelium 53, 54. Due to the fact that there are no animal studies for inflammatory neuropathies and that cell differentiation in the current study was based on morphological aspects, it is speculative to specify which immunological subtype was counted.…”

Section: Discussionsupporting

confidence: 64%

Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy

Stettner

Hinrichs

Guthoff

et al. 2015

Ann Clin Transl Neurol

105

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ObjectiveThere is an unmet need for better diagnostic tools to further delineate clinical subsets of heterogeneous chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) to facilitate treatment decisions. Corneal confocal microscopy (CCM) is a noninvasive and reproducible nerve imaging technique. This study evaluates the potential of CCM as a diagnostic surrogate in CIDP and MMN.MethodsIn a cross‐sectional prospective approach, 182 patients and healthy controls were studied using CCM to quantify corneal nerve damage and immune cell infiltration.ResultsPatients with CIDP and MMN had a reduction in corneal nerve fiber (CNF) measures and an increase in corneal immune cell infiltrates. In CIDP, CNF parameters decreased with increasing duration of disease. The number of dendritic cells in proximity to CNFs was increased in patients with early disease and correlated with the degree of motor affection. A further reduction in CNF parameters and an increase in nondendritic cells were observed in patients with painful neuropathy. In CIDP patients with antineuronal antibodies the number of nondendritic cells was increased.InterpretationOur findings suggest that CNF loss may reflect severity of neuropathy and quantification of distinct cells around the CNF plexus may help in stratifying CIDP subtypes, clinical course, and disease activity. However, further longitudinal studies are required before CCM can be considered as a valid surrogate endpoint for patients with CIDP and MMN.

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Section: Discussionsupporting

confidence: 64%

Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy

Stettner

Hinrichs

Guthoff

et al. 2015

Ann Clin Transl Neurol

105

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“…However, central SP cells neither showed stem cell characteristics, nor were ABCG2 positive, indicating that several types of transporters may take part in Hoechst33342 dye efflux in the rat cornea (111). In addition, the presence of ABCG2 positive, slow cycling Langerhans cells was demonstrated in the limbal basal epithelium of rats, implying that cells sorted based on ABCG2 expression or Hoechst dye exclusion may yield a heterogeneous population of rat limbal stem cells (113).…”

Section: Isolation Of Lescmentioning

confidence: 94%

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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“…The mouse has no K3 [86] but K12, which normally pairs with K3, is present and expression is restricted to the cornea [87] , as shown in Figure 3B. Several authors have also noted that cell morphology of cells in the basal limbal epithelium was more characteristic of stem cells (smaller, euchromatin-rich, high nucleus to cytoplasm ratio) than the corneal epithelium [3,88] but, as already noted, Langerhans cells in the limbus also share this phenotype [56] . These observations are consistent with the hypothesis that the limbus contains stem cells but no more than that.…”

Section: Stem Cell Markers and Phenotypementioning

confidence: 94%

“…It has been estimated that once cells leave the basal corneal epithelial layer the time to cell loss (turnover time) is only about 7 d (range 3 1 /2 to 14 d) for mice, rats and humans [45,[47][48][49][50] but a longer turnover time of between 14 and 21 d has been estimated for rabbits [51] . Most investigations have identified label-retaining cells in the basal limbal epithelium but not in the corneal epithelium either after wounding [5,13] or during normal homeostasis in mice [13,45,[52][53][54] , rats [55,56] and rabbits [57] . Two caveats about the exclusive location of label-retaining cells to the limbus in these experiments should be mentioned: (1) species differences in cell cycle kinetics and technical differences between studies may affect the number of cells that remain labelled so the chase period needs to be optimised for each species (for example, in these studies, chase periods for treatments without wounding varied from 4 to 11 wk); (2) using a relatively short chase period of 4 wk, Chen et al [56] showed that approximately 20% of the label-retaining cells were slow-cycling Langerhans cells rather than putative slow-cycling stem cells.…”

Section: Cell Division Characteristics and Identification Of Slow-cycmentioning

confidence: 99%

“…Most investigations have identified label-retaining cells in the basal limbal epithelium but not in the corneal epithelium either after wounding [5,13] or during normal homeostasis in mice [13,45,[52][53][54] , rats [55,56] and rabbits [57] . Two caveats about the exclusive location of label-retaining cells to the limbus in these experiments should be mentioned: (1) species differences in cell cycle kinetics and technical differences between studies may affect the number of cells that remain labelled so the chase period needs to be optimised for each species (for example, in these studies, chase periods for treatments without wounding varied from 4 to 11 wk); (2) using a relatively short chase period of 4 wk, Chen et al [56] showed that approximately 20% of the label-retaining cells were slow-cycling Langerhans cells rather than putative slow-cycling stem cells. (These Langerhans cells also shared two other characteristics of putative stem cells, discussed below, as they were positive for the marker ABCG2 and had a high nucleus to cytoplasm ratio).…”

Section: Cell Division Characteristics and Identification Of Slow-cycmentioning

confidence: 99%

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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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Existence of small slow-cycling Langerhans cells in the limbal basal epithelium that express ABCG2

Cited by 50 publications

References 29 publications

Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy

Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy

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

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

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