Corneal stem cells in review (original) (raw)
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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 Repair and Regeneration: Current Concepts and Future Directions
Frontiers in Bioengineering and Biotechnology, 2019
The cornea is a unique tissue and the most powerful focusing element of the eye, known as a window to the eye. Infectious or non-infectious diseases might cause severe visual impairments that need medical intervention to restore patients' vision. The most prominent characteristics of the cornea are its mechanical strength and transparency, which are indeed the most important criteria considerations when reconstructing the injured cornea. Corneal strength comes from about 200 collagen lamellae which criss-cross the cornea in different directions and comprise nearly 90% of the thickness of the cornea. Regarding corneal transparency, the specific characteristics of the cornea include its immune and angiogenic privilege besides its limbus zone. On the other hand, angiogenic privilege involves several active cascades in which anti-angiogenic factors are produced to compensate for the enhanced production of proangiogenic factors after wound healing. Limbus of the cornea forms a border between the corneal and conjunctival epithelium, and its limbal stem cells (LSCs) are essential in maintenance and repair of the adult cornea through its support of corneal epithelial tissue repair and regeneration. As a result, the main factors which threaten the corneal clarity are inflammatory reactions, neovascularization, and limbal deficiency. In fact, the influx of inflammatory cells causes scar formation and destruction of the limbus zone. Current studies about wound healing treatment focus on corneal characteristics such as the immune response, angiogenesis, and cell signaling. In this review, studied topics related to wound healing and new approaches in cornea regeneration, which are mostly related to the criteria mentioned above, will be discussed.
BioMed Research International, 2015
Objective. To evaluate outcomes of cultivated limbal epithelial transplantation (CLET) for management of ocular surface failure due to limbal stem cell deficiency (LSCD).Design. Prospective, noncomparative, interventional case series and extensive comparison with recent similar studies.Participants. Twenty eyes with LSCD underwent CLET (11 autologous; 9 allogeneic) and were followed up for 3 years. Etiologies were divided into 3 prognostic categories: Group 1, chemical injuries (7 eyes); Group 2, immune-based inflammation (4 eyes); and Group 3, noninflammatory diseases (9 eyes).Intervention. Autologous and allogeneic limbal epithelial cells were cultivated on amniotic membranes and transplanted. Evaluations were based on clinical parameters, survival analysis, and in vivo confocal microscopy (IVCM). European Union Tissues/Cells Directive and good manufacturing procedures were followed.Main Outcome Measures. Improved clinical parameters, absence of epithelial defects, and improved ce...
Stem cell-based therapeutic strategies for corneal epithelium regeneration
Churchill Livingstone, 2021
Any significant loss of vision or blindness caused by corneal damages is referred to as corneal blindness. Corneal blindness is the fourth most common cause of blindness worldwide, representing more than 5% of the total blind population. Currently, corneal transplantation is used to treat many corneal diseases. In some cases, implantation of artificial cornea (keratoprosthesis) is suggested after a patient has had a donor corneal transplant failure. The shortage of donors and the side effects of keratoprosthesis are limiting these approaches. Recently, researchers have been actively pursuing new approaches for corneal regeneration because of these limitations. Nowadays, tissue engineering of different corneal layers (epithelium, stroma, endothelium, or full thickness tissue) is a promising approach that has attracted a great deal of interest from researchers and focuses on regenerative strategies using different cell sources and biomaterials. Various sources of corneal and non-corneal stem cells have shown significant advantages for corneal epithelium regeneration applications. Pluripotent stem cells (embryonic stem cells and iPS cells), epithelial stem cells (derived from oral mucus, amniotic membrane, epidermis and hair follicle), mesenchymal stem cells (bone marrow, adipose-derived, amniotic membrane, placenta, umbilical cord), and neural crest origin stem cells (dental pulp stem cells) are the most promising sources in this regard. These cells could also be used in combination with natural or synthetic scaffolds to improve the efficacy of the therapeutic approach. As the ocular surface is exposed to external damage, the number of studies on regeneration of the corneal epithelium is rising. In this paper, we reviewed the stem cell-based strategies for corneal epithelium regeneration.
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 Stem-Cell Therapy and Long-Term Corneal Regeneration
New England Journal of Medicine, 2010
Corneal renewal and repair are mediated by stem cells of the limbus, the narrow zone between the cornea and the bulbar conjunctiva. Ocular burns may destroy the limbus, causing limbal stem-cell deficiency. We investigated the long-term clinical results of cell therapy in patients with burn-related corneal destruction associated with limbal stem-cell deficiency, a highly disabling ocular disease.
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.
Cell Based Therapy for Ocular Surface Reconstruction
Ocular surface reconstruction involves an entire gamut of modalities, both medical and surgical. The principal goals of medical therapy would be supplementation of the tear film, suppression of inflammation, limitation of tissue destruction and promotion of epithelial wound healing. The surgical approaches and techniques are varied and often performed as staged procedures. In this communication, we discuss the principles in the approach to the management of limbal stem cell deficiency disorders. Relevant anatomy of the ocular surface The ocular surface functional unit consists of stratified squamous corneal epithelium, limbal epithelium covering the junction between corneal and conjunctival epithelium, mucin producing conjunctival epithelium, muco-cutaneous junction of the lids which helps in the proper spread of the tear film, lipid secreting meibomian glands, aqueous secreting lacrimal glands and functioning eyelids. It acts as an interface between the eye and the outer world and is unique that it is not protected by skin. The normal functioning of the ocular surface requires an adequate tear film, normal ocular adnexa, normal corneal sensitivity and functioning limbal stem cells and hence a normal corneal epithelium (Figure 1). The limbus predominantly has two functions. It acts as a barrier between the avascular, smooth, non-keratinized and goblet cell-free corneal epithelium and a mucin secreting, goblet cell rich conjunctival epithelium. It is also the source of regenerating epithelial cells, from the stem cells, and helps in maintaining of the corneal epithelium 1-4. Stem cells, present in all self-renewing tissues, are a small subpopulation of specialized undifferentiated, self-renewing cells with a slow cell cycle, long life span, a high capacity for error-free self renewal and a capability for asymmetric division 1-4. They are capable of indefinite Figure 1: Figure showing the ocular surface which includes the tear film, eyelashes, eyelid margins, meibomian glands and epithelial surfaces of conjunctiva and cornea Figure 2: (Left) Anatomy of the limbus and the lineage of 'Stem cells'; (Right) XYZ hypothesis
Concise Review: Stem Cells for Corneal Wound Healing
STEM CELLS
Corneal wound healing is a complex process that occurs in response to various injuries and commonly used refractive surgery. It is a significant clinical problem, which may lead to serious complications due to either incomplete (epithelial) or excessive (stromal) healing. Epithelial stem cells clearly play a role in this process, whereas the contribution of stromal and endothelial progenitors is less well studied. The available evidence on stem cell participation in corneal wound healing is reviewed, together with the data on the use of corneal and non-corneal stem cells to facilitate this process in diseased or postsurgical conditions. Important aspects of corneal stem cell generation from alternative cell sources, including pluripotent stem cells, for possible transplantation upon corneal injuries or in disease conditions are also presented.
2020
Objectives: This study compares the efficacy of stem cell transplantation in corneal regeneration and restoration of the limbic deficit in an experimental chemical burn in rabbits. Methods: The biopsy of limbus and the chemical burn were performed in all rabbits, and the amniotic membranes were obtained from a pregnant rabbit. A control group without transplantation, to study spontaneous and natural healing, and transplanted the stem cells produced in vitro under the corneal epithelium burned. To compare the result, a group was tested for amniotic stem cell transplantation, a group for limbal stem cell graft, and another group for combined transplantation of both types of stem cells. Results: Transplanted rabbits develop permanent unilateral blindness due to a severe limbic deficit. The group receiving only amniotic stem cells shows temporary anatomical improvement without functional recovery. The two groups receiving limbal stem cells alone or combined with amniotic stem cells show...