The Limbal Epithelial Progenitors in the Limbal Niche Environment
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Abstract:
Limbal epithelial progenitors are stem cells located in limbal palisades of vogt.In this review, we present the audience with recent evidence that limbal epithelial progenitors may be a powerful stem cell resource for the cure of human corneal stem cell deficiency.Further understanding of their mechanism may shed lights to the future successful application of stem cell therapy not only to the eye tissue, but also to the other tissues in the human body.Keywords:
Stem cell niche
Limbal stem cell
Recent reports have demonstrated the expression of intercellular adhesion molecule-1 (ICAM-1; CD54) on the epithelium in various allergic diseases and inflammatory conditions, including the bronchial epithelium of patients with allergic asthma, conjunctival epithelium of allergic patients after allergen-specific challenge, and corneal epithelium of rejected corneal allografts. We investigated the presence of ICAM-1 expression on the corneal epithelium from a patient with vernal keratoconjunctivitis (VKC). Immunohistochemical staining of the diseased cornea demonstrated abundant ICAM-1 expression on the corneal epithelium. Immunoreactive ICAM-1 appeared to localize primarily to the cells of the basal and middle layers of the corneal epithelium. No staining was detected on the ocular surface epithelium. The normal, healthy cornea demonstrated no significant ICAM-1 expression on any of the epithelial layers, similar to that previously reported. To the best of our knowledge, this is the first report of ICAM-1 expression on the corneal epithelium from a patient with VKC
Vernal keratoconjunctivitis
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It is difficult to maintain corneal epithelial cells for several passages in culture. At a first step to establish a culture system for corneal epithelium, the authors evaluated factors which seemed to be involved in the growth kinetics and mitotic activity of rabbit corneal epithelium in vitro. First of all, to compare the growth kinetics of peripheral and central epithelium, we measured the areas and distances of the epithelium that outgrew from peripheral and central explants in culture. The peripheral corneal epithelium grew 1.2-to 1.6-fold better than the central corneal epithelium. However, there was no significant difference between them. Secondly, we evaluated the effects of epidermal growth factor (EGF), cholera toxin (CTX) and insulin, which were contained in supplemented hormonal epithelial medium (SHEM) developed by Jumblatt et al, on the mitotic activity of rabbit corneal epithelium. Among these drugs, only EGF had the ability to increase the epithelial cell number after 10 days of incubation. By contrast, CTX which elevated the level of cyclic AMP inhibited the proliferation of the epithelium.
Organ culture
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Abstract. After removing a circular area of the central corneal epithelium of the rat eye, the labelling indices and the mitotic rates were measured at various times after wounding, both in the cornea and in the adjacent conjunctival epithelium. The proliferative response was most marked in the corneal epithelium adjacent to the wound, but there was also a definite response in the epithelium covering the denuded areas, and in the conjunctival epithelium. The study demonstrated that the conjunctiva itself plays a role in the healing of a central corneal epithelial wound. The similarities in the cellular response may indicate that both epithelia are under the influence of the same growth‐suppressing factors (chalones), and must be looked upon as a unit. However, no support was found for the theory that the limbal area serves as a generative organ for the corneal epithelium.
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Several aspects of the ocular surface epithelium, including its clinical appearance, its effect on the strength of underlying stromal wounds, and its healing rates, have been compared between regenerating epithelium of conjunctival and that of corneal origin in rabbits. The results showed that conjunctival epithelium could not transform completely into functionally competent corneal epithelium within 6 weeks.
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Stem cell niche
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After 6 hr of oxygen deprivation, the human corneal epithelium had not swollen. Over the first hour of recovery from anoxia, the epithelium shrank by up to 20% before returning toward its predeprivation thickness. No fluorescein staining of the epithelium was seen during these experiments, but some subjects were able to discern halos immediately after deprivation. We conclude that homeostasis is maintained in the corneal epithelium for up to 6 hr of anoxia, but the intercellular spaces may be altered.
Homeostasis
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Stem cell niche is the microenvironment in which stem cells reside,and it is essential for stem cells self-renewal and differentiation. Tumor stem cells which live in abnormal niche control tumor genesis,and appropriate niche can promote tumor growth and metastasis. Altering unique niche can suppress and affect malignant phenotypes of tumor.
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Tumor stem cells: Neoolastie processes: Niche
Stem cell niche
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Abstract Stem cells contain intrinsic mechanisms that control their behaviour but the environment immediately surrounding them, known as the niche, also plays a fundamental role. In a host of tissues and organisms the stem cell niche has been shown to maintain stem cells in an undifferentiated state and to regulate their behaviour. This stem cell – niche principle is typified by the corneal limbus. When limbal epithelial stem cells (LESC) are dissociated from their niche in the limbal palisades of Vogt they rapidly differentiate and cease to function as stem cells. It might be imagined that an understanding of the LESC niche would be of the highest priority for researchers in this field but the existence of a surrogate niche, in the form of growth arrested 3T3 fibroblast feeder layers, has allowed research on LESC biology to progress in the absence of a thorough understanding of their native niche. Thankfully LESC niche research has been gathering momentum and several exciting developments hold promise for limbal stem cell deficient patients. Amongst these are the characterisation of the physical structure of the niche and the identification of mesenchymal niche cells, which themselves displaying stem cell properties.
Stem cell niche
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1. An autoradiographic study was made of the regenerative mechanism of the corneal epithelium of albino rabbits.2. Regeneration of the corneal epithelium is achieved not only by migration of the epithelial cells from the non-injured area but also by active mitosis in the basal cells of the regenerating epithelium of the injured area.3. The area adjacent to the wound edge contributes an important share to the regeneration of the epithelium in the form of DNA synthetic cell band.4. 3H-cytidine is incorporated into the nuclei as well as into the cytoplasms of all the cells of the normal rabbit corneal epithelium.
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