Corneal epithelial stem cells in health and disease (original) (raw)

In sickness and in health: Corneal epithelial stem cell biology, pathology and therapy

Experimental eye research, 2010

Our window to the world is provided by the cornea on the front surface of the eye. The integrity and functionality of the outermost corneal epithelium is essential for vision. A population of limbal epithelial stem cells (LESCs) are responsible for maintaining the epithelium throughout life by providing a constant supply of daughter cells that replenish those constantly lost from the ocular surface during normal wear and tear and following injury. LESC deficiency leads to corneal opacification, inflammation, vascularization and discomfort (Daniels et al., 2001, 2007). Cultured LESC delivery is one of several examples of successful adult stem cell therapy in patients. The clinical precedence for use of stem cell therapy and the accessibility of the transparent stem cell niche make the cornea a unique model for the study of adult stem cells in physiological conditions as well as in disease.

Corneal Stem Cells as a Source of Regenerative Cell-Based Therapy

Stem Cells International

In the past few years, intensive research has focused on corneal stem cells as an unlimited source for cell-based therapy in regenerative ophthalmology. Today, it is known that the cornea has at least two types of stem cells: limbal epithelial stem cells (LESCs) and corneal stromal stem cells (CSSCs). LESCs are used for regeneration of corneal surface, while CSSCs are used for regeneration of corneal stroma. Until now, various approaches and methods for isolation of LESCs and CSSCs and their successful transplantation have been described and tested in several preclinical studies and clinical trials. This review describes in detail phenotypic characteristics of LESCs and CSSCs and discusses their therapeutic potential in corneal regeneration. Since efficient and safe corneal stem cell-based therapy is still a challenging issue that requires continuous cooperation between researchers, clinicians, and patients, this review addresses the important limitations and suggests possible strat...

Corneal Stem Cells: Bridging the Knowledge Gap

Stem cell research offers hope to countless patients whose conditions have heretofore been deemed incurable. Better understanding of stem cell behaviors and functions will lead to insights into biological mysteries encompassing the fields of angiogenesis, development, tissue homeostasis, wound healing, and carcinogenesis. Clarity of vision requires smooth ocular surface on which the corneal epithelial cells undergo continuous turnover every 3 to 10 days. Tragically, many patients are blinded and devastated by severe ocular surface diseases due to limbal stem cell deficiency even though, besides opaque cornea, their eyes are otherwise healthy. Corneal stem cell transplantation offers hope by creating clear windows for these eyes; unfortunately, the long-term successful outcome remains limited. The nature of corneal epithelial stem cell is poorly understood, but many circumstantial evidences suggest the presence of "source cells" in the limbal region of the eye. Nonetheless, the precise biomarker of corneal stem cell remains elusive. The stem cell puzzle can be solved with application of the fundamental scientific method-asking salient questions at the right time and finding answers using keen observations and proper tools. Readily accessibility and structural simplicity of the cornea lend themselves to study of the stem cell biology. The ability to identify and isolate corneal stem cell will be a gateway to meaningful investigation into its biology. This advance will also have direct impact on improving the efficacy of promising stem-cell-based therapies, including limbal stem cell transplantation.

Concise review: the coming of age of stem cell treatment for corneal surface damage

Stem cells translational medicine, 2014

The cornea is a vital component of the eye because it provides approximately 70% of the refraction and focusing of incoming light. Being the outermost surface of the eye, it faces continuous stress from dryness, photodamage, infection, and injury; however, like the skin, the cornea regularly refreshes itself by shedding its epithelial cells, which are readily replaced, keeping the ocular surface stable and functional. This regular turnover of the corneal epithelial cells occurs through the stem cells in the limbus, an annular ring of a tissue surrounding the cornea, separating it from the sclera and the conjunctival membrane. The loss of this reserve of stem cells leads to a condition called limbal stem cell deficiency. Treatment for this disorder has evolved from transplanting whole limbal tissues to the affected eye to transplanting laboratory cultured limbal cells. This procedure is called cultivated limbal epithelial transplantation (CLET). Since its start in 1997, more than 1,0...

Corneal epithelial stem cells: deficiency and regulation

Stem cell reviews, 2008

The corneal epithelium is continuously renewed by a population of stem cells that reside in the corneoscleral junction, otherwise known as the limbus. These limbal epithelial stem cells (LESC) are imperative for corneal maintenance with deficiencies leading to in-growth of conjunctival cells, neovascularisation of the corneal stroma and eventual corneal opacity and visual loss. One such disease that has traditionally been thought to be due to LESC deficiency is aniridia, a pan-ocular congenital eye disease due to mutations in the PAX6 gene. Corneal changes or aniridia related keratopathy (ARK) seen in aniridia are typical of LESC deficiency. However, the pathophysiology behind ARK is still ill defined, with current theories suggesting it may be caused by a deficiency in the stem cell niche and adjacent corneal stroma, with altered wound healing responses also playing a role (Ramaesh et al, International Journal of Biochemistry & Cell Biology 37:547–557, 2005) or abnormal epidermal differentiation of LESC (Li et al., The Journal of Pathology 214:9, 2008). PAX6 is considered the master control gene for the eye and is required for normal eye development with expression continuing in the adult cornea, thus inferring a role for corneal repair and regeneration (Sivak et al., Developments in Biologicals 222:41–54, 2000). Studies of models of Pax6 deficiency, such as the small eyed (sey) mouse, should help to reveal the intrinsic and extrinsic mechanisms involved in normal LESC function.

Repairing the corneal epithelium using limbal stem cells or alternative cell-based therapies

Expert opinion on biological therapy, 2018

The corneal epithelium is maintained by limbal stem cells (LSCs) that reside in the basal epithelial layer of the tissue surrounding the cornea termed the limbus. Loss of LSCs results in limbal stem cell deficiency (LSCD) that can cause severe visual impairment. Patients with partial LSCD may respond to conservative therapies designed to rehabilitate the remaining LSCs. However, if these conservative approaches fail or, if complete loss of LSCs occurs, transplantation of LSCs or their alternatives is the only option. While a number of clinical studies utilizing diverse surgical and cell culture techniques have shown favorable results, a universal cure for LSCD is still not available. Knowledge of the potential risks and benefits of current approaches, and development of new technologies, is essential for further improvement of LSCD therapies. Areas covered: This review focuses on cell-based LSCD treatment approaches ranging from current available clinical therapies to preclinical st...

Limbal Epithelial Stem Cells in Corneal Regeneration

Delhi Journal of Ophthalmology, 2013

The cornea is the transparent and outer most part of the eye, which is responsible for clear vision. The homeostasis of corneal epithelium is maintained by stem cells (SCs) located at the limbus, which is a transitional zone between cornea and conjunctiva. Due to some conditions limbal stem cells (LSCs) can be destroyed or lost and this can cause limbal stem cell deficiency (LSCD). Conventional non-surgical management and corneal transplants are not enough to treat LSCD. Recent advances in tissue engineering have made possible to rejuvenate the LSC deficit ocular surface with ex-vivo cultivated limbal epithelium and this is possible to achieve from a significantly small limbal biopsy. In spite of all progress made in this field, it is still questionable to identify LSCs based on the biomarkers. This review article will focus on the biology of LSCs and their emerging trend in the field of regenerative medicine. Apart from that this article will also highlight different culture techniques to cultivate LSCs and novel biofunctional scaffolds.

Corneal stem cells in review

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

The cornea provides the eye with protection and the refractive properties essential for visual acuity. The transparent epithelium is highly specialized with basal and stratified squamous cells that are renewed throughout life from a stem cell population. The stem cells are thought to reside at the corneal limbus and may be maintained by a variety of intrinsic and extrinsic factors such as the local environment, survival factors, and cytokines. A number of markers have been localized to the limbus in an attempt to identify stem cells; however, definite stem cell identification remains elusive. During homeostasis and following injury to the corneal epithelium, the limbal stem cells divide to produce daughter transient amplifying cells that proliferate, migrate, and differentiate to replace lost cells. However, this cannot occur if the stem cell population is depleted. Limbal stem cell deficiency then results in corneal re-epithelialization by the neighboring conjunctiva, causing pain, poor vision, and even blindness. This review will focus on corneal epithelial stem cells in ocular surface repair and regeneration. The current knowledge of stem cell biology in the corneal epithelium, clinical consequences of stem cell deficiency, and therapeutic strategies aimed at reversing stem cell deficiency will be discussed. (WOUND REP REG 2001;9:483-494) From the Epithelial Repair and Regeneration Group a , There are several examples in the animal kingdom of the Kingdom. ability to regenerate tissue following injury. The newt, to regenerate whole arms and legs; however, we are able EC1V 9EL, UK. Fax: ‫ם‬ 44 (0) 20 7608 6887; Email: