13 years of cultured limbal epithelial cell therapy: A review of the outcomes

Baylis, Oliver; Figueiredo, Francisco C; Henein, Christin; Lako, Majlinda; Ahmad, Sajjad

doi:10.1002/jcb.23028

Cited by 227 publications

(236 citation statements)

References 48 publications

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“…A detailed summary of the outcomes of CLET, updated in 2011, was published by Baylis et al [16], and a summary of the controversies and challenges of this therapy, also updated in 2011, was published by O'Callaghan and Daniels [17]. The primary measure of success in treatment for LSCD is the clinical presence of a stable ocular surface with no superficial corneal vascularization, conjunctivalization, or repeat epithelial breakdown.…”

Section: Outcomes Of Cletmentioning

confidence: 99%

Concise Review: The Coming of Age of Stem Cell Treatment for Corneal Surface Damage

Ramachandran

Basu

Sangwan

et al. 2014

Stem Cells Translational Medicine

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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 1,000 CLET procedures have been reported from around the world, with varying degrees of success. In this paper, we compare the methods of cultivation and the outcomes and discuss some problem areas, use of other cells as substitutes for limbal epithelium, and various carrier materials used in transplantation. Our analysis suggests that CLET as a treatment for corneal surface damage has come of age. We also highlight a simpler procedure (simple limbal epithelial transplantation) that involves cultivation of limbal tissue in situ on the surface of the cornea in vivo and that has outcomes comparable to CLET.

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Section: Outcomes Of Cletmentioning

confidence: 99%

Concise Review: The Coming of Age of Stem Cell Treatment for Corneal Surface Damage

Ramachandran

Basu

Sangwan

et al. 2014

Stem Cells Translational Medicine

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“…These cases can be treated with transplantation of cultured LESCs either derived by a biopsy from the patient's healthy eye (in the case of unilateral injury) or harvested from donor tissue (LESC allograft) (Baylis et al 2011;Shortt et al 2010). There has been a clinical observation that pterygium, a condition where fibrotic tissue from the conjunctiva invades the cornea in a characteristic triangular shape, usually occurs in the nasal limbus (Kanski 2003).…”

Section: Introductionmentioning

confidence: 99%

The impact of age on the physical and cellular properties of the human limbal stem cell niche

Notara¹,

Shortt

O’Callaghan³

et al. 2012

AGE

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The limbal niche in the corneoscleral junction of the eye, habitat of the limbal epithelial stem cells (LESC), facilitates corneal epithelial regeneration by providing physical support and chemical signalling. Anatomical structures within the limbus, namely, limbal epithelial crypts and focal stromal projections, are believed to function as a putative niche for LESCs. In this study, the impact of age on the topography of this niche was investigated. Also, the relationship between niche topography and limbal epithelial cell phenotype was assessed. Ex vivo imaging of the limbus in cadaveric tissue of donors aged from infancy to 90 years was carried out using electron and confocal microscopy. The data suggested that the area occupied by the crypts was sharply reduced after the age of 60 years. The niche microstructures also became smoother with donor age. The phenotypic assessment of cultured limbal epithelial cells harvested from donors of different ages showed that the levels of putative stem cell markers as well as telomerase activity and telomere length remained unchanged, regardless of niche topography. However, the colony forming efficiency of the cultures was significantly reduced with age (p<0.05). This is the first comprehensive study of the effect of age on the structural and phenotypic characteristics of the human limbal niche. The results have a significant biological value as they suggest a correlation of limbal architecture with decline of re-epithelialisation rate in older patients. Overall, the data also suggest that LESCs harvested from younger donors may be more suitable for cultured LESC therapy production.

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“…2,6 This condition termed as limbal stem cell deficiency (LSCD) can arise from a variety of etiologies, both inherited and acquired, 6 most commonly by burns and acid and alkali injuries. 7 As the epithelium of donor corneas has a short lifespan, LSCD patients cannot be successfully treated by PKP. [8][9][10][11][12] Unilateral LSCD can be successfully treated with autologous keratolimbal grafts of 2-3 clock hours size (about 25% of the limbus) taken from the healthy fellow eye.…”

Section: Introductionmentioning

confidence: 99%

Plasma Polymer-Coated Contact Lenses for the Culture and Transfer of Corneal Epithelial Cells in the Treatment of Limbal Stem Cell Deficiency

Brown

Low

Mariappan

et al. 2014

Tissue Engineering Part A

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Extensive damage to the limbal region of the cornea leads to a severe form of corneal blindness termed as limbal stem cell deficiency (LSCD). Whereas most cases of corneal opacity can be treated with full thickness corneal transplants, LSCD requires stem cell transplantation for successful ocular surface reconstruction. Current treatments for LSCD using limbal stem cell transplantation involve the use of murine NIH 3T3 cells and human amniotic membranes as culture substrates, which pose the threat of transmission of animal-derived pathogens and donor tissue-derived cryptic infections. In this study, we aimed to produce surface modified therapeutic contact lenses for the culture and delivery of corneal epithelial cells for the treatment of LSCD. This approach avoids the possibility of suture-related complications and is completely synthetic. We used plasma polymerization to deposit acid functional groups onto the lenses at various concentrations. Each surface was tested for its suitability to promote corneal epithelial cell adhesion, proliferation, retention of stem cells, and differentiation and found that acid-based chemistries promoted better cell adhesion and proliferation. We also found that the lenses coated with a higher percentage of acid functional groups resulted in a higher number of cells transferred onto the corneal wound bed in rabbit models of LSCD. Immunohistochemistry of the recipient cornea confirmed the presence of autologous, transplanted 5-bromo-2¢-deoxyuridine (BrdU)-labeled cells. Hematoxylin staining has also revealed the presence of a stratified epithelium at 26 days post-transplantation. This study provides the first evidence for in vivo transfer and survival of cells transplanted from a contact lens to the wounded corneal surface. It also proposes the possibility of using plasma polymer-coated contact lenses with high acid functional groups as substrates for the culture and transfer of limbal cells in the treatment of LSCD.

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13 years of cultured limbal epithelial cell therapy: A review of the outcomes

Cited by 227 publications

References 48 publications

Concise Review: The Coming of Age of Stem Cell Treatment for Corneal Surface Damage

Concise Review: The Coming of Age of Stem Cell Treatment for Corneal Surface Damage

The impact of age on the physical and cellular properties of the human limbal stem cell niche

Plasma Polymer-Coated Contact Lenses for the Culture and Transfer of Corneal Epithelial Cells in the Treatment of Limbal Stem Cell Deficiency

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