Induction of Epithelial Progenitors In Vitro from Mouse Embryonic Stem Cells and Application for Reconstruction of Damaged Cornea in Mice

Homma, R.; Yoshikawa, Hideshi; Takeno, Mitsuhiro; Kurokawa, Manae S.; Masuda, Chieko; Takada, Erika; Tsubota, Kazuo; Ueno, Satoki; Suzuki, Noboru

doi:10.1167/iovs.04-0044

Cited by 92 publications

(70 citation statements)

References 47 publications

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“…1B). On the basis of these results and those of previous publications that have used collagen IV to differentiate corneal epithelial cells from mESCs [22], it was decided to use collagen IV-coated plates to differentiate the hESC cells in the subsequent studies.…”

Section: Effects Of Extracellular Matrix On the Differentiation Of Hementioning

confidence: 99%

“…For these reasons, collagen IV, laminin, and fibronectin were investigated for their suitability at directing the differentiation of hESC into corneal epithelial-like cells and/or maintenance of newly generated corneal epithelial progenitors in culture. Indeed, previous studies have already shown that collagen IV can be used to differentiate mESC into corneal epithelial cells [22]. Limbal fibroblasts form the major cellular component of the limbal stroma upon which the LSCs reside [7,8], and they produce specific cytokines that promote corneal epithelial wound healing by the LSCs [7].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, skin-like epithelial cells have been differentiated from ESC using various methods [22][23][24][25][26][27]. The first differentiation methods have relied heavily on coculture with human fibroblasts or 3T3 mouse embryonic fibroblast-derived ECM to drive the differentiation of mESC into skin epithelial cells [23,24].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, it has been shown that cells expressing cytokeratin (CK) 12, a marker specific to terminally differentiated cells (TDCs) of the corneal epithelium, can be obtained by plating mESC onto collagen IV [22]. Moreover, transplantation of such 8-day-old differentiation cultures onto the surface of a cornea denuded of its epithelium results in the formation of an epithelium with morphological similarities to corneal epithelium 24 hours post-transplant, suggesting that functional corneal cells can be obtained from murine ESCs [22].…”

Section: Introductionmentioning

confidence: 99%

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Differentiation of Human Embryonic Stem Cells into Corneal Epithelial-Like Cells by In Vitro Replication of the Corneal Epithelial Stem Cell Niche

et al. 2007

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Human embryonic stem cells (hESCs) are pluripotent cells capable of differentiating into any cell type of the body. It has long been known that the adult stem cell niche is vital for the maintenance of adult stem cells. The cornea at the front of the eye is covered by a stratified epithelium that is renewed by stem cells located at its periphery in a region known as the limbus. These so-called limbal stem cells are maintained by factors within the limbal microenvironment, including collagen IV in basement membrane and limbal fibroblasts in the stroma. Because this niche is very specific to the stem cells (rather than to the more differentiated cells) of the corneal epithelium, it was hypothesized that replication of these factors in vitro would result in hESC differentiation into corneal epithelial-like cells. Indeed, here we show that culturing of hESC on collagen IV using medium conditioned by the limbal fibroblasts results in the loss of pluripotency and differentiation into epithelial-like cells. Further differentiation results in the formation of terminally differentiated epithelial-like cells not only of the cornea but also of skin. Scanning electron microscopy shows that some differences exist between hESC-derived and adult limbal epithelial-like cells, necessitating further investigation using in vivo animal models of limbal stem cell deficiency. Such a model of hESC differentiation is useful for understanding the early events of epithelial lineage specification and to the eventual potential application of epithelium differentiated from hESC for clinical conditions of epithelial stem cell loss.

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Section: Effects Of Extracellular Matrix On the Differentiation Of Hementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differentiation of Human Embryonic Stem Cells into Corneal Epithelial-Like Cells by In Vitro Replication of the Corneal Epithelial Stem Cell Niche

et al. 2007

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“…These cultured cells were generally applied to the recipient eye as an intact cell sheet (either on amniotic membrane, fibrin, or alone) [26-31, 44, 48]. However, bone marrow-derived stem cells have also been administered via systemic injection and injection under transplanted amniotic membrane [32,33], and embryonic stem cells were applied as a cell suspension [45]. Injection of mesenchymal stem cells under amniotic membrane did not provide an improved corneal surface compared to controls with conjunctivalization and vascularization of the cornea occurring in treated eyes [33].…”

Section: Alternative Stem Cell Sourcesmentioning

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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Oral Mucosa Tissue Equivalents for the Treatment of Limbal Stem Cell Deficiency

et al. 2020

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Cultured limbal and oral epithelial cells have been successfully used to treat patients with limbal stem cell deficiency (LSCD). The most common culture method for these cell therapies utilises amniotic membrane as a cell support and/ or murine 3T3s as feeder fibroblasts. The aim of this study was to refine the production of autologous oral mucosal cell therapy for the treatment of LSCD. Real Architecture for 3D Tissue (RAFT) was used as an alternative cell culture support. In addition, oral mucosal cells (epithelial and fibroblast) were used as autologous alternatives to donor human limbal epithelial cells (HLE) and murine 3T3s. The following tissue equivalents were produced and characterised: firstly, for patients with bilateral LSCD, an oral mucosal tissue

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Induction of Epithelial Progenitors In Vitro from Mouse Embryonic Stem Cells and Application for Reconstruction of Damaged Cornea in Mice

Cited by 92 publications

References 47 publications

Differentiation of Human Embryonic Stem Cells into Corneal Epithelial-Like Cells by In Vitro Replication of the Corneal Epithelial Stem Cell Niche

Differentiation of Human Embryonic Stem Cells into Corneal Epithelial-Like Cells by In Vitro Replication of the Corneal Epithelial Stem Cell Niche

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

Oral Mucosa Tissue Equivalents for the Treatment of Limbal Stem Cell Deficiency

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