Ex vivo expansion of limbal epithelial stem cells: amniotic membrane serving as a stem cell niche

Grueterich, Martin; Espana, Edgar M.; Tseng, Scheffer C.G.

doi:10.1016/j.survophthal.2003.08.003

Cited by 245 publications

(143 citation statements)

References 80 publications

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“…The above clinical discovery has led others to successfully transplant such an ex vivo expanded human limbal epithelial tissue to treat human corneas with total limbal SC deficiency [34,99,100]. Because no murine 3T3 fibroblast feeder layer is needed, human amniotic membrane may serve as an ex vivo surrogate niche (for review see [39]). Because the resultant epithelial phenotype is "limbal" when expanded on an intact amniotic membrane, which retains the devitalized amniotic epithelial cells, but is "corneal" when expanded on an epithelially-denuded amniotic membrane [101], we began to explore the idea that human amniotic epithelial cells may serve as a better non-xenogenic surrogate niche to support limbal epithelial SCs [Chen et al, manuscript submitted, 2006].…”

Section: Will Restoration Of Niche Support Be Critical For Ex Vivo Exmentioning

confidence: 99%

“…These new advances collectively make the corneal/limbal epithelia a prime tissue to practice regenerative medicine. For more detailed information on the aforementioned progresses regarding limbal epithelial SCs, the reader is encouraged to consult several reviews [35][36][37][38][39][40][41][42][43][44][45]. Further understanding of how self-renewal and fate decision of limbal epithelial SCs are regulated will undoubtedly unravel their additional therapeutic potentials in the future.…”

Section: Introductionmentioning

confidence: 99%

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Niche regulation of corneal epithelial stem cells at the limbus

et al. 2007

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Among all adult somatic stem cells, those of the corneal epithelium are unique in their exclusive location in a defined limbal structure termed Palisades of Vogt. As a result, surgical engraftment of limbal epithelial stem cells with or without ex vivo expansion has long been practiced to restore sights in patients inflicted with limbal stem cell deficiency. Nevertheless, compared to other stem cell examples, relatively little is known about the limbal niche, which is believed to play a pivotal role in regulating self-renewal and fate decision of limbal epithelial stem cells. This review summarizes relevant literature and formulates several key questions to guide future research into better understanding of the pathogenesis of limbal stem cell deficiency and further improvement of the tissue engineering of the corneal epithelium by focusing on the limbal niche.

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Section: Will Restoration Of Niche Support Be Critical For Ex Vivo Exmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Niche regulation of corneal epithelial stem cells at the limbus

et al. 2007

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“…The use of human amniotic membrane instead of 3T3 cells, as well as replacement of FCS with the patients' autologous serum in the culture media was introduced by some groups (118,119,122). The human amniotic membrane (AM) may be intact (iAM, containing devitalized amniotic epithelium) or denuded (dAM, without epithelium) (123).…”

Section: Culturing Of Lescmentioning

confidence: 99%

“…Probably the same applies for dAM as well, since limbal epithelial cells cultured on iAM showed a less differentiated phenotype (exhibiting less cytokeratin3, connexin43 and 50 expression by immunostaining and immunoblots) than those cultured on dAM, with an intermediate degree of differentiation of LESCs on dAM in the presence of 3T3 feeder cells (131). The evident, although limited growth supporting ability of human amniotic membrane may be owed to its growth factors and basement membrane components, many of which, including NGF, KGF, HGF, bFGF, TGFb, and integrins b1 and b4 have been shown to be present in the limbal epithelium and stroma as well [reviewed in (123)]. Moreover, AM also has anti-inflammatory and antiangiogenic effects (132).…”

Section: Culturing Of Lescmentioning

confidence: 99%

Stem cells of the adult cornea: From cytometric markers to therapeutic applications

et al. 2008

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The cornea is a major protective shield of the interior of the eye and represents two thirds of its refractive power. It is made up of three tissue layers that have different developmental origins: the outer, epithelial layer develops from the ectoderm overlying the lens vesicle, whereas the stroma and the endothelium have mesenchymal origin. In the adult organism, the outermost corneal epithelium is the most exposed to environmental damage, and its constant renewal is assured by the epithelial stem cells that reside in the limbus, the circular border of the cornea. Cell turnover in the stromal layer is very slow and the endothelial cells probably do not reproduce in the adult organism. However, recent experimental evidence indicates that stem cells may be found in these layers. Damage to any of the corneal layers leads to loss of transparency and low vision. Corneal limbal stem cell deficiency results in severe ocular surface disease and its treatment by transplantating ex vivo expanded limbal epithelial cells is becoming widely accepted today. Stromal and endothelial stem cells are potential tools of tissue engineering and regenerative therapies of corneal ulcers and endothelial cell loss. In the past few years, intensive research has focused on corneal stem cells aiming to improve the outcomes of the current corneal stem cell transplantation techniques. This review summarizes the current state of knowledge on corneal epithelial, stromal and endothelial stem cells. Special emphasis is placed on the molecular markers that may help to identify these cells, and the recently revealed mechanisms that could maintain their ''stemness'' or drive their differentiation. The techniques for isolating and culturing/ expanding these cells are also described. '

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“…Esses fatores ambientais incluem a matriz extracelular do limbo, particularmente a membrana basal, interações célula-matriz e contato célu-la-célula. O estroma do limbo subjacente que contém células estromais e vasos sanguíneos deve também regular a função das células tronco pela liberação de fatores de crescimento (9,(23)(24) . Embora as características específicas de tais nichos não estejam completamente conhecidas, a manipulação de alguns dos seus componentes, incluindo proteínas da matriz extracelular e fatores de crescimento, já tem começado a ser explorada.…”

Section: Discussionunclassified