الفهرس 
Stem Cells BasicsOnly 14 pages are availabe for public view
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Abstract
Stem cells are undifferentiated cells able to divide indefinitely yet maintain the ability to differentiate into specific cell types. They are able to survive throughout the lifetime of the organism, while maintaining their number, producing populations of daughter cells that can proceed down unique pathways of differentiation.
The cornea is the primary refractive element at the anterior surface of the eye. It is most unique in being both avascular and transparent so as to allow the light to be transmitted to the retina. The transparency of the cornea and therefore visual acuity is dependent upon the integrity and functionality of its epithelium.
A population of adult stem cells called limbal stem cells (LSCs) is responsible for replenishing the corneal epithelium throughout life by providing a constant supply of daughter cells that replace those constantly removed from the ocular surface during normal wear and tear and following injury.
The limbus is the transition zone between the cornea, conjunctiva and sclera, where the corneal epithelium merges with that of the conjunctiva. LSCs reside in the basal layer of the limbal epithelium in a stem cell niche, which maintains them in their undifferentiated state. This stem cell niche is represented by ”the palisades of Vogt”, which are believed to provide a protective environment for the LSCs. The palisades of Vogt consist of a series of radially oriented papillae-like structures located in the sub-epithelial connective tissue.
When LSCs are destroyed or the limbal stem cell niche is dysfunctional, a pathological state known as limbal stem cell deficiency (LSCD) emerges.
Many hereditary or acquired diseases and injurious conditions can cause LSCD. Corneal diseases associated with LSCD can be subdivided into two major categories. In the first category, there is an identifiable factor that has caused direct damage to the LSCs such as chemical or thermal burn, Stevens-Johnson syndrome, multiple surgeries and cryotherapies, contact lens wear, severe microbial infections, and radiation. A second category is characterized by a gradual loss of the LSC population without a known or identifiable precipitating factor, and in this group a loss of the limbal stromal niche may be the primary disease mechanism. This category includes conditions such as aniridia, peripheral ulcerative keratitis, as well as idiopathic LSCD.
When LSCD occurs, the neighbouring conjunctival epithelium, which is normally prevented from encroaching onto the corneal surface by the LSCs, migrates to cover the corneal surface in a process known as conjunctivalization. Limbal stem cell deficient corneas also carry other pathological features, such as destruction of the basement membrane, emergence of superficial neovascularization, chronic stromal inflammation, and scarring. Therefore, LSCD constitutes one major type of ocular surface failure leading to corneal blindness.
Depending on the extent of limbal involvement, LSCD can be partial or total. In partial LSCD, there is localized deficiency of LSCs in a region of the limbus, which results in sectoral ingrowth of conjunctival epithelium in this region. In total LSCD, dysfunction or destruction of the entire LSC population occurs resulting in conjunctivalization of the entire cornea.
LSCD is manifested by decreased vision, photophobia, tearing, blepharospasm, and recurrent episodes of pain (epithelial breakdown), as well as a history of chronic inflammation with redness. The clinical signs include: vascularization and opacification of the cornea, and in severe cases scarring, keratinization, and calcification of the cornea may occur. Among all signs of LSCD, only conjunctivalization is specific for the diagnosis. The other signs, can also be observed in many other corneal diseases without LSCD.
The clinical clues of conjunctivalization can be detected by the loss of limbal palisades of Vogt under slit-lamp examination or by late fluorescein staining of the cornea, which reflects poor epithelial barrier function. Definitive detection of conjunctivalization relies on impression cytology; specimens can be stained with periodic acid schiff to identify goblet cells on the corneal surface, which are useful in confirming the diagnosis. The use of monoclonal antibodies to cytokeratin 3 (CK3) and cytokeratin 19 (CK19) confirms a conjunctival phenotype (CK3−/CK19+).
LSCD can be managed with autologous or allogenic transplantation of LSCs. Systemic immunosuppression is required with allotransplantation. It is essential to determine whether LSCD is partial or total, and ideally all associated ocular abnormalities if present should be addressed before limbal transplantation.
For partial LSCD, sequential sector conjunctival epitheliectomy (SSCE) is the procedure to be considered first, but a sector limbal transplant (SLT) may be required. Amniotic membrane transplantation (AMT) alone can restore damaged corneal surfaces by aiding the expansion of residual LSCs in vivo. Ipsilateral limbal autograft translocation is another option for the treatment of partial LSCD, this process involves removing a stem cell graft from the healthy portion of the limbus and transferring it to the stem cell deficient part in the same eye.
For total LSCD, a population of LSCs must be supplied in order to restore stable corneal epithelium. In total unilateral LSCD, conjunctival limbal autograft transplantation (CLAU) is the procedure of choice, where an autologous limbal tissue is transferred from the unaffected fellow eye to the stem cell deficient eye. In total bilateral LSCD, the use of allografts from living-related donors (LRD) or cadaveric donors (CD) is the only option.
Ex vivo expansion of limbal derived cells is an important option in the surgical management of total LSCD both unilateral and bilateral. Biopsies taken from the unaffected eye or from LRD can be used to extract epithelial cells, or can be applied directly as explants on culture plates to generate stratified sheets for transplantation.
Oral mucosa epithelial stem cells and hair follicle-derived epithelial stem cells can be used as alternative autologous epithelial stem cells for limbal stem cell transplantation (LSCT). Mesenchymal stem cells and embryonic stem cells may also be promising source of cells for re-epithelialization of the cornea.
It could be concluded that the use of limbal stem cells with or without ex vivo expansion is very promising in treating cases of corneal diseases associated with limbal stem cell deficiency. Other stem cells as oral mucosa epithelial stem cells, hair follicle-derived epithelial stem cells, mesenchymal stem cells and embryonic stem cells are also promising which raises hope to restore sight in patients inflicted with limbal stem cell deficiency.