Cultured Autologous Oral Mucosal Epithelial Cell Sheet (CAOMECS) Transplantation for the Treatment of Corneal Limbal Epithelial Stem Cell Deficiency

Burillon, C.; Huot, Laure; Justin, V.; Nataf, Serge; Chapuis, François; Decullier, Évelyne; Damour, O.

doi:10.1167/iovs.11-7744

Cited by 160 publications

(127 citation statements)

References 26 publications

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“…In the meantime, transplantation of in vitro cultured nonocular autologous oral mucosal epithelium has been used in patients with bilateral limbal cell deficiency, particularly for acute chemical burns. This procedure can give satisfactory results (Burillon et al, 2012;Chen et al, 2009) and provide adequate re-epithelialization and stabilization of the surface of the cornea if the cultured autologous thin sheets (with a few cells' worth of thickness) of oral mucosal epithelium are lifted with temperature sensitive cell sheet-lifting technology that preserves the cultured cell-cell junctions and an intact basement membrane for transplantation (Burillon et al, 2012). This method appears to prevent the vascularization and loss of corneal opacity previously associated with oral mucosal transplants that often had multiple epithelial layers of stratification and numerous mucosal cell structures (Chen et al, 2009).…”

Section: Limbal Stem Cellsmentioning

confidence: 85%

Stem Cell Therapies in Clinical Trials: Progress and Challenges

2015

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Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types. To date, there have been few reports of safety issues arising from autologous or allogeneic transplants. Many cells administered show transient presence for a few days with trophic influences on immune or inflammatory responses. Limbal stem cells have been registered as a product for eye burns in Europe and mesenchymal stem cells have been approved for pediatric graft versus host disease in Canada and New Zealand. Many other applications are progressing in trials, some with early benefits to patients.

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Section: Limbal Stem Cellsmentioning

confidence: 85%

Stem Cell Therapies in Clinical Trials: Progress and Challenges

2015

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“…32 This problem may be circumvented by performing oral mucosal graft as a limbal surrogate 33 or ex vivo expansion of oral mucosal epithelial SCs, 34 especially for eyes where transplantation of allogeneic limbal SCs has failed or is not feasible. 35,36 …”

Section: Introductionmentioning

confidence: 99%

Niche Regulation of Limbal Epithelial Stem Cells: Relationship between Inflammation and Regeneration

Tseng

Zhang

et al. 2016

The Ocular Surface

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Human limbal palisades of Vogt are the ideal site for studying and practicing regenerative medicine due to their accessibility. Nonresolving inflammation in limbal stroma is common manifestation of limbal stem cell (SC) deficiency and presents as a threat to the success of transplanted limbal epithelial SCs. This pathologic process can be overcome by transplantation of cryopreserved human amniotic membrane (AM), which exerts anti-inflammatory, antiscarring and anti-angiogenic action to promote wound healing. To determine how AM might exert anti-inflammation and promote regeneration, we have purified a novel matrix, HC-HA/PTX3, responsible for the efficacy of AM efficacy. HC-HA complex is covalently formed by hyaluronan (HA) and heavy chain 1 (HC1) of inter-α-trypsin inhibitor by the catalytic action of tumor necrosis factor-stimulated gene-6 (TSG-6) and are tightly associated with pentraxin 3 (PTX3) to form HC-HA/PTX3. In vitro reconstitution of the limbal niche can be established by reunion between limbal epithelial progenitors and limbal niche cells on different substrates. In 3-dimensional Matrigel, clonal expansion indicative of SC renewal is correlated with activation of canonical Wnt signaling and suppression of canonical BMP signaling. In contrast, SC quiescence can be achieved in HC-HA/PTX3 by activation of canonical BMP signaling and non-canonical planar cell polarity (PCP) Wnt signaling, but suppression of canonical Wnt signaling. HC-HA/PTX3 is a novel matrix mitigating nonresolving inflammation and restoring SC quiescence in the niche for various applications in regenerative medicine.

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“…To find a proper substitutive cell source of LSCs, researchers also explored the potential of using oral mucosal epithelia and adult stem cells, such as hair follicle stem cells and marrow mesenchymal stem cells in LSCD cases and received several encouraging results. [11][12][13][14][15] However, all these sources have their own limitations. Because of the lack of antiangiogenic factors expression, the peripheral corneal neovascularization was observed frequently in COMET.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13] However, all these sources have their own limitations. Some studies proved that cultivated oral mucosal epithelium transplantation (COMET) efficiently repaired the wound cornea in some LSCD cases in a few years, 14,15 but other long-term clinical observations showed that the peripheral corneal neovascularization could be frequently observed after COMET because of the lack of antiangiogenic factors expression, such as sFlt-1, TIMP-3, and TSP-1, in these transplanted cells. 16 And for patients with pemphigoid, Steven Johnson syndrome, and pemphigus, which could influence or destroy oral mucosa, COMET was also unsuitable.…”

Section: Introductionmentioning

confidence: 99%

Reconstruction of Functional Ocular Surface by Acellular Porcine Cornea Matrix Scaffold and Limbal Stem Cells Derived from Human Embryonic Stem Cells

Zhu

Zhang

Sun

et al. 2013

Tissue Engineering Part A

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Limbal stem cells (LSCs) derived from human embryonic stem cells (hESCs) hold great potential for cell-based therapies for ocular surface diseases. The cell-based therapies mainly depend on an appropriate differentiation proposal with a high efficiency and on a suitable scaffold. In this study, we aimed to establish a feasible and efficient strategy for inducing hESCs into LSC-like cells by the LSC conditioned medium. The induced cells possessed the similar morphologic characteristics and expression of normal LSCs and showed a strong clonogenic and proliferative capacity in vitro. To construct a tissue-engineering corneal graft, these differentiated cells were seeded on an acelluar porcine corneal matrix (APCM), which maintained the corneal basement membrane in vitro. After 14 days culture, these induced cells gave rise to stratified epithelial cell sheets on the APCM and the basal cells still kept LSC characteristics. In rabbit total limbal stem cell deficiency (LSCD) models, the tissue-engineering graft had the potential to reconstruct the damaged ocular surface and alleviated the invasion of corneal neovascularization. These findings indicated that the engraftment constructed with the APCM scaffold and hESC-derived LSCs might be a potential therapy option for ocular surface regeneration in LSCD cases.

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Cultured Autologous Oral Mucosal Epithelial Cell Sheet (CAOMECS) Transplantation for the Treatment of Corneal Limbal Epithelial Stem Cell Deficiency

Abstract: CAOMECS is a well-tolerated and safe tissue-engineered product. These results suggest its efficacy for reconstructing the ocular surface in patients with total bilateral corneal LSCD.

Cited by 160 publications

References 26 publications

Stem Cell Therapies in Clinical Trials: Progress and Challenges

Stem Cell Therapies in Clinical Trials: Progress and Challenges

Niche Regulation of Limbal Epithelial Stem Cells: Relationship between Inflammation and Regeneration

Reconstruction of Functional Ocular Surface by Acellular Porcine Cornea Matrix Scaffold and Limbal Stem Cells Derived from Human Embryonic Stem Cells

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