Review paper Clinical applications of limbal epithelial stem cells (original) (raw)
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The limbal epithelium of the eye - A review of limbal stem cell biology, disease and treatment
BioEssays, 2013
The limbus is a narrow band of tissue that encircles the cornea, the transparent 'window' into the eye. The outermost layer of the cornea is the epithelium, which is necessary for clear vision. The limbus acts as a 'reservoir' for limbal stem cells which maintain and regenerate the corneal epithelium. It also functions as a barrier to the conjunctiva and its blood vessels. Limbal stem cell deficiency is a general term for diseases which are characterised by the impairment of the limbus, limbal stem cells and their ability to replenish the corneal epithelium through proliferation and differentiation. Consequently, sufferers experience chronic pain and progressive blindness. This paper will highlight the salient milestones of limbal stem cell biology and potential future treatments for limbal stem cell deficiency.
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.
The Role of Limbal Stem Cells in Corneal Epithelial Maintenance
Ophthalmology, 2009
To study and characterize the epithelial cells in patients with a central "island" of normal epithelial cells surrounded with 360°of clinically apparent limbal stem cell (SC) deficiency with conjunctivalization of the limbus and peripheral cornea.
Chapter 5 Limbal Stem Cells: Application in Ocular Biomedicine
International review of cell and molecular biology
Corneal opacification due to limbal stem cell deficiency (LSCD) is an important cause for ocular morbidity, resulting from a number of intrinsic and extrinsic factors. While the extrinsic factors include conditions such as chemical or thermal injuries, intrinsic include dysfunction, or reduction in the number of stem cells either due to pathological changes in autoimmune diseases or secondary to certain clinical conditions such as diabetes, dry eye disorders, or multiple previous eye surgeries. LSCD is characterized by a classic triad of signs—conjunctivalization, neovascularization and decrease in vision. With the increasing knowledge of limbal stem cells, the treatment of this condition has evolved from simple debridement to use of biological materials, direct transplantation of the healthy limbal tissue from the contralateral eye, or allogenic source to the use of cultivated limbal epithelial sheets. This chapter provides an update on the disease pathology, various treatment meth...
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...
PloS one, 2017
Epithelial and stromal stem cells are required to maintain corneal transparency. The aim of the study was to develop a new method to isolate and grow both corneal stromal (SSC) and epithelial limbal (LSC) stem cells from small human limbal biopsies under culture conditions in accordance with safety requirements mandatory for clinical use in humans. Superficial limbal explants were retrieved from human donor corneo-scleral rims. Human limbal cells were dissociated by digestion with collagenase A, either after epithelial scraping or with no scraping. Isolated cells were cultured with Essential 8 medium (E8), E8 supplemented with EGF (E8+) or Green's medium with 3T3 feeder-layers. Cells were characterized by immunostaining, RT-qPCR, colony forming efficiency, sphere formation, population doubling, second harmonic generation microscopy and differentiation potentials. LSC were obtained from unscraped explants in E8, E8+ and Green's media and were characterized by colony formation...
Limbal stem cells in health and disease
Bioscience Reports, 2001
Stem cells are present in all self-reviewing tissues and have unique properties. The ocular surface is made up of two distinct types of epithelial cells, constituting the conjunctival and the corneal epithelia. These epithelia are stratified, squamous and non-keratinized. Although anatomically continuous with each other at the corneoscleral limbus, the two cell phenotypes represent quite distinct subpopulations. The stem cells for the cornea are located at the limbus. The microenvironment of the limbus is considered to be important in maintaining stemness of the stem cells. They also act as a ''barrier'' to conjunctival epithelial cells and prevent them from migrating on to the corneal surface. In certain pathologic conditions, however, the limbal stem cells may be destroyed partially or completely resulting in varying degrees of stem cell deficiency with its characteristic clinical features. These include ''conjunctivalization'' of the cornea with vascularization, appearance of goblet cells, and an irregular and unstable epithelium. The stem cell deficiency can be managed with auto or allotransplantation of these cells. With the latter option, systemic immunosuppression is required. The stem cells can be expanded ex ûiûo on a processed human amniotic membrane and transplanted back to ocular surface with stem cell deficiency without the need of immunosuppression.
Cells
Limbal stem cells constitute an important cell population required for regeneration of the corneal epithelium. If insults to limbal stem cells or their niche are sufficiently severe, a disease known as limbal stem cell deficiency occurs. In the absence of functioning limbal stem cells, vision-compromising conjunctivalization of the corneal epithelium occurs, leading to opacification, inflammation, neovascularization, and chronic scarring. Limbal stem cell transplantation is the standard treatment for unilateral cases of limbal stem cell deficiency, but bilateral cases require allogeneic transplantation. Herein we review the current therapeutic utilization of limbal stem cells. We also describe several limbal stem cell markers that impact their phenotype and function and discuss the possibility of modulating limbal stem cells and other sources of stem cells to facilitate the development of novel therapeutic interventions. We finally consider several hurdles for widespread adoption of...
The Phenotype of Limbal Epithelial Stem Cells
2007
PURPOSE. The purpose of this study was to identify phenotypic markers of human limbal stem cells in fetal and adult corneas. METHODS. RNA from microscopically dissected superficial limbal and central fetal (18 weeks) corneas was amplified and used to generate P 32 -labeled, reverse-transcribed antisense RNA that was linearly amplified and hybridized to a focused stem cell cDNA microarray. Differential gene expression of fetal limbus was compared with the expression of central cornea. Microarray differential expression experiments were performed on P63-expressing primary cultured limbal epithelial cells (passage 1; Pa1) and primary cells passaged 5 times (Pa5). Semiquantitative RT-PCR assay and immunohistochemistry were performed on fetal and adult corneas and cultured primary limbal epithelial cells, to confirm the results of the microarray experiments. Slow-cycling (pulsed bromodeoxyuridine label-retaining) limbal epithelium in corneal organ culture was studied for the expression of four selected upregulated limbal genes. RESULTS. Of the 266 genes tested, 33 were differentially overexpressed (more than twofold) in the fetal limbus (compared with central cornea) and primary cultured limbal epithelium compared with primary cells after 5 passages. Cytokeratin 15 (CK15) and cytokeratin 14 (CK14) are expressed in limbal basal epithelium and P-cadherin (CDH3) and Wnt-4 expression was restricted to basal and immediate parabasal limbal epithelium of both the adult and fetal corneas). Bromodeoxyuridine label retaining epithelium in corneal organ culture (slow-cycling cells) expressed the four selected limbal upregulated genes. CONCLUSIONS. For the first time, a focused stem cell pathway microarray analysis has been performed on fetal cornea and cultured limbal explant epithelium. CK15, CK14, CDH3, and Wnt-4 are expressed in the basal limbal epithelial cells. (Invest Ophthalmol Vis Sci.
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.