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Tissue engineered corneal epithelium derived from clinical-grade human embryonic stem cells.
He, Jia; Ou, Shangkun; Ren, Jun; Sun, Huimin; He, Xin; Zhao, Zhongyang; Wu, Han; Qu, Yangluowa; Liu, Tingting; Jeyalatha, Vimalin; Zhang, Liying; Li, Qiyuan; Reinach, Peter Sol; Quantock, Andrew; Hao, Jie; Liu, Zuguo; Li, Wei.
Afiliação
  • He J; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Ou S; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Ren J; School of Informatics, Xiamen University, Xiamen, Fujian, China; National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, Fujian, China.
  • Sun H; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • He X; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Zhao Z; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Wu H; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Qu Y; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Liu T; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Jeyalatha V; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Zhang L; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Li Q; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.
  • Reinach PS; Wenzhou Medical University, Department of Ophthalmology, Wenzhou, Zhejiang, China; Wenzhou Medical University, Department of Optometry, Wenzhou, Zhejiang, China.
  • Quantock A; Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom.
  • Hao J; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China; National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing, China. Elect
  • Liu Z; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.; Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China; Xiamen University Affiliated Xiamen Eye Center, Xiamen,
  • Li W; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, China.; Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China; Xiamen University Affiliated Xiamen Eye Center, Xiamen,
Ocul Surf ; 18(4): 672-680, 2020 10.
Article em En | MEDLINE | ID: mdl-32710961
ABSTRACT

PURPOSE:

To construct tissue engineered corneal epithelium from a clinical-grade human embryonic stem cells (hESCs) and investigate the dynamic gene profile and phenotypic transition in the process of differentiation.

METHODS:

A stepwise protocol was applied to induce differentiation of clinical-grade hESCs Q-CTS-hESC-1 and construct tissue engineered corneal epithelium. Single cell RNA sequencing (scRNA-seq) analysis was performed to monitor gene expression and phenotypic changes at different differentiation stages. Immunostaining, real-time quantitative PCR and Western blot analysis were conducted to detect gene and protein expressions. After subcutaneous transplantation into nude mice to test the biosafety, the epithelial construct was transplanted in a rabbit corneal limbal stem cell deficiency (LSCD) model and followed up for eight weeks.

RESULTS:

The hESCs were successfully induced into epithelial cells. scRNA-seq analysis revealed upregulation of ocular surface epithelial cell lineage related genes such as TP63, Pax6, KRT14, and activation of Wnt, Notch, Hippo, and Hedgehog signaling pathways during the differentiation process. Tissue engineered epithelial cell sheet derived from hESCs showed stratified structure and normal corneal epithelial phenotype with presence of clonogenic progenitor cells. Eight weeks after grafting the cell sheet onto the ocular surface of LSCD rabbit model, a full-thickness continuous corneal epithelium developed to fully cover the damaged areas with normal limbal and corneal epithelial phenotype.

CONCLUSION:

The tissue engineered corneal epithelium generated from a clinical-grade hESCs may be feasible in the treatment of limbal stem cell deficiency.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Limbo da Córnea / Epitélio Corneano / Doenças da Córnea / Células-Tronco Embrionárias Humanas Tipo de estudo: Guideline Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Limbo da Córnea / Epitélio Corneano / Doenças da Córnea / Células-Tronco Embrionárias Humanas Tipo de estudo: Guideline Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article