Stem Cells and Ocular Regeneration

Attico, Eustachio; Chiavelli, Chiara; Sceberras, Virginia; Fantacci, Monica; Melonari, M.; Pellegrini, Graziella

doi:10.1016/b978-0-12-801238-3.65456-9

Cited by 4 publications

(3 citation statements)

References 14 publications

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“…Limbal stem cells (LSCs) play a major role in ocular surface homeostasis and are responsible for corneal regeneration, achieved through centripetal cell migration and differentiation from the limbus to the central cornea [1]. As a result of acquired (chemical/thermal burns) or genetic conditions, these cells can be partially or entirely lost, resulting in a pathology known as Limbal Stem Cell Deficiency (LSCD), where corneal opacity and conjunctivalization lead to visual impairment and blood vessels migration, otherwise absent over the central cornea [2,3].…”

Section: Introductionmentioning

confidence: 99%

Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up

Attico,

Galaverni,

Torello

et al. 2023

IJMS

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Total bilateral Limbal Stem Cell Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated oral mucosa epithelial transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although abnormal peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa has been challenging. Previously proposed markers were shown to be co-expressed by different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cultured holoclones, identifying Paired Like Homeodomain 2 (PITX2) as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up corneal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors that were differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of transplanted corneas.

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Section: Introductionmentioning

confidence: 99%

Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up

Attico,

Galaverni,

Torello

et al. 2023

IJMS

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show abstract

“…The ocular surface is the first passage for the light and acts as an anatomical barrier for the eye against external pathogens. It is comprised of closely integrated regions that form a unique functional unit, comprehensive of different tissues [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

SOX2 Is a Univocal Marker for Human Oral Mucosa Epithelium Useful in Post-COMET Patient Characterization

Attico

Galaverni

Bianchi

et al. 2022

IJMS

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Total bilateral Limbal Stem Cells Deficiency is a pathologic condition of the ocular surface due to loss or impairment of corneal stem cell function, altering homeostasis of the corneal epithelium. Cultivated Oral Mucosa Epithelial Transplantation (COMET) is the only autologous treatment for this pathology. During the follow-up, a proper characterization of the transplanted oral mucosa on the ocular surface supports understanding the regenerative process. The previously proposed markers for oral mucosa identification (e.g., keratins 3 and 13) are co-expressed by corneal and conjunctival epithelia. Here, we propose a new specific marker to distinguish human oral mucosa from the epithelia of the ocular surface. We compared the transcriptome of holoclones (stem cells) from the human oral mucosa, limbal and conjunctival cultures by microarray assay. High expression of SOX2 identified the oral mucosa vs. cornea and conjunctiva, while PAX6 was highly expressed in corneal and conjunctival epithelia. The transcripts were validated by qPCR, and immunological methods identified the related proteins. Finally, the proposed markers were used to analyze a 10-year follow-up aniridic patient treated by COMET. These findings will support the follow-up analysis of COMET treated patients and help to shed light on the mechanism of corneal repair and regeneration.

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“…In its basal layers, the limbus hosts the so-called palisades of Vogts, which are optimal niche for LESCs. The palisades of Vogts comprise melanocytes, stromal fibroblasts, immune cells, and other epithelial non-stem cells that support the progenitor cells [1,2].…”

Section: Introductionmentioning

confidence: 99%

Clinical Studies of COMET for Total LSCD: a Review of the Methods and Molecular Markers for Follow-Up Characterizations

Attico

Galaverni

Pellegrini

2021

Curr Ophthalmol Rep

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Purpose of Review This review outlines the main features of the clinical trials where cultivated oral mucosa epithelial cell transplantation (COMET) was performed, aiming to underscore a link between the clinical outcome and the expression of specific markers during the follow-up of patients, characteristic for a defined epithelium (cornea, oral mucosa, or conjunctiva) or related to vascularization. Recent Findings Currently, little is known about the reasons underlying the success or failure of COMET. To address this issue, we focused on tissue characterization at the molecular level, highlighting the findings concerning angiogenesis. Summary There are several discrepancies in the outcomes of COMET clinical trials. While some corneal/conjunctival markers can be considered reliable for understanding the biological mechanisms that drive corneal repair after transplants, a unique marker specifically expressed in the oral mucosa and an accurate study of the vascularization processes are currently missing. Together, these insights will help forecast successes and failures of these technologies. KeywordsOral mucosa . Cornea . Cultivated oral mucosa epithelial cell transplantation (COMET) . Cultivated autologous oral mucosal epithelial cell sheet (CAOMECS) . Total bilateral limbal stem cell deficiency (LSCD) . Biomarkers This article is part of the Topical Collection on Cornea * Eustachio Attico

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Stem Cells and Ocular Regeneration

Cited by 4 publications

References 14 publications

Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up

Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up

SOX2 Is a Univocal Marker for Human Oral Mucosa Epithelium Useful in Post-COMET Patient Characterization

Clinical Studies of COMET for Total LSCD: a Review of the Methods and Molecular Markers for Follow-Up Characterizations

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