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

Notara, Maria; Alatza, Argyro; Gilfillan, J.; Harris, A. R.; Levis, Hannah J.; Schrader, Stefan; Vernon, Amanda; Daniels, Julie T.

doi:10.1016/j.exer.2009.09.023

Cited by 102 publications

(107 citation statements)

References 88 publications

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“…These abnormalities often occur simultaneously and affect each other to promote disease progression. The development of corneal irregularities, such as thickening of the epithelial layer as well as stromal neovascularization and inflammation, compromises corneal transparency and results in blindness (reviewed in Cursiefen 2007;Notara et al 2010). In the case of tumor pathology, hyperproliferative tissue is provided a means of survival and metastasis by invading blood vessels signaled for growth by tumor tissue and its associated inflammatory cells (reviewed in Allavena et al 2008).…”

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confidence: 99%

A Pathogenic Relationship Between a Regulator of the Actin Cytoskeleton and Serum Response Factor

et al. 2010

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Cell hyperproliferation, inflammation, and angiogenesis are biological processes central to the pathogenesis of corneal disease, as well as other conditions including tumorigenesis and chronic inflammatory disorders. Due to the number of disease conditions that arise as a result of these abnormalities, identifying the molecular mechanisms underlying these processes is critical. The avascular and transparent cornea serves as a good in vivo model to study the pathogenesis of cell hyperproliferation, inflammation, and angiogenesis. Corneal disease 1 (Dstn corn1 ) mice are homozygous for a spontaneous null allele of the destrin (Dstn) gene, which is also known as actin depolymerizing factor (ADF). These mice exhibit abnormalities in the cornea including epithelial cell hyperproliferation, stromal inflammation, and neovascularization. We previously identified that the transcription factor, serum response factor (SRF) and a number of its target genes are upregulated in the cornea of these mice. In this study, we show that conditional ablation of Srf in the corneal epithelium of a diseased Dstn corn1 cornea results in the rescue of the epithelial cell hyperproliferation, inflammation, and neovascularization phenotypes, delineating an epithelial cell-specific role for SRF in the development of all of these abnormalities. Our study also demonstrates that Dstn is genetically upstream of Srf and defines a new functional role for SRF as the master regulator of a hyperproliferative, inflammatory phenotype accompanied by neovascularization.

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confidence: 99%

A Pathogenic Relationship Between a Regulator of the Actin Cytoskeleton and Serum Response Factor

et al. 2010

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“…Our focus is on disorders that result in loss or dysfunction of the adult corneal epithelial stem cells normally residing at the limbus, at least in humans (Notara et al, 2010;Ordonez & Girolamo, 2012;Joe & Yeung, 2014). A number of biomaterials have been assessed as scaffolds (Feng et al, 2014) for transfer of corneal epithelial stem cells and transient-amplifying cells to the ocular surface (Joe & Yeung, 2014), and silk fibroin shows promise for corneo-limbal reconstruction (Harkin et al, 2011;Bray et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye

Irani

Tian

Wang

et al. 2015

Experimental Eye Research

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Abbreviations: BSS ophthalmic balanced salt solution; DMEM Dulbecco's Modified Eagle's Medium; EGF epidermal growth factor; FBS fetal bovine serum; FDA fluorescein diacetate; PBS phosphate buffered saline; PCL polycaprolactone; pSi nanostructured porous silicon; SEM scanning electron microscopy; TEM transmission electron microscopy. To investigate loading of large-molecule biologics, murine BALB/c 3T3 cells, responsive to epidermal growth factor, insulin and transferrin, were seeded on composite materials. The cells showed significantly more proliferation at 48 h when seeded on composites loaded with these biologics, than on unloaded composites. No cell proliferation was observed on PCL alone, indicating the biologics had loaded into the pSi microparticles. Drug release, measured by ELISA for insulin, indicated a burst followed by a slower, continuous release over six days. When implanted under the rat conjunctiva, the most promising composite material did not cause significant neovascularization but did elicit a macrophage and mild foreign body

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“…Features of stem cells such as small cell size and high nuclear to cytoplasmic ratio can also be used to aid the identification of putative LESCs. These markers have been reviewed elsewhere [13][14][15].…”

Section: Challenges and Controversiesmentioning

confidence: 99%

“…At present, the gold standard culture method for limbal epithelial cells for use in the clinic uses mouse 3T3 fibroblasts as a feeder layer and bovine serum. At present, the 3T3 coculture system seems to be optimal for the expansion of LESCs [13] and is allowed for clinical use until a suitable alternative is found. It has been suggested that this concern over the use of the 3T3s as a feeder layer is exaggerated; as very few 3T3s remain on the final graft, these cells are growth arrested and therefore could not engraft, and there is no evidence that these cells have had a harmful effect from their use in graft production [25].…”

Section: Challenges and Controversiesmentioning

confidence: 99%

Concise Review: Limbal Epithelial Stem Cell Therapy: Controversies and Challenges

O’Callaghan

Daniels

2011

Stem Cells

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Limbal epithelial stem cells (LESCs) are a population of stem cells responsible for maintenance and repair of the corneal surface. Injury and disease can result in a deficiency of these stem cells, the vision affecting condition called limbal stem cell deficiency (LSCD) in which the cornea becomes opaque, vascularized, and inflamed. Cultured LESC therapy was first described in 1997, and LESCs cultured from either patients or donors have been used to successfully treat LSCD. In this review, some of the challenges and controversies associated with cultured LESC therapy will be discussed including alternative stem cell sources.

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

Cited by 102 publications

References 88 publications

A Pathogenic Relationship Between a Regulator of the Actin Cytoskeleton and Serum Response Factor

A Pathogenic Relationship Between a Regulator of the Actin Cytoskeleton and Serum Response Factor

A novel pressed porous silicon-polycaprolactone composite as a dual-purpose implant for the delivery of cells and drugs to the eye

Concise Review: Limbal Epithelial Stem Cell Therapy: Controversies and Challenges

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