Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors

Background: Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progeni...

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Main Authors: Bandeira, Francisco, Goh, Tze-Wei, Setiawan, Melina, Yam, Gary Hin-Fai, Mehta, Jodhbir Singh
Other Authors: School of Materials Science and Engineering
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Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/146997
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spelling sg-ntu-dr.10356-1469972023-07-14T15:58:55Z Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors Bandeira, Francisco Goh, Tze-Wei Setiawan, Melina Yam, Gary Hin-Fai Mehta, Jodhbir Singh School of Materials Science and Engineering Science::Biological sciences Corneal Epithelium Limbal Stem Cell Deficiency Background: Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET). Methods: STEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry. Tissue-engineered (TE) MET-Epi cells on fibrin gel were transplanted to corneal surface of the rat LSCD model caused by alkali injury. Epithelial healing, corneal edema, and haze grading, CE formation were assessed by fluorescein staining, slit lamp bio-microscopy, anterior segment optical coherence tomography, and immunohistochemistry. Results: CD73high/CD90high/CD105high/CD166high/CD14negative/CD31negativehuman ADSC underwent MET, giving viable epithelial-like progenitors expressingδNp63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-β4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epicells expressing cell junction proteins ZO1 and occludin. When transplanted onto rat corneal surface with LSCD-induced PED, TE-MET-Epi achieved more efficient epithelial healing, suppressed corneal edema, and opacities, when compared to corneas without treatment or transplanted with TE-ADSC. CE markers (CK3, 12, and CDH1) were expressed on TE-MET-Epi-transplanted corneas but not in other control groups. Conclusion: Human ADSC-derived epithelial-like cells, via MET, recovered the CE from PED associated with LSCD. ADSC can be a viable adult stem cell source for potential autologous epithelial cell-based therapy for corneal surface disorders. Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version Singapore National Research Foundation under its Translational and Clinical Research (TCR) program (NMRC/TCR/008-SERI/2013) and Clinician Scientist Award-Senior Investigator Category (JRNMRR163801), National Medical Research Council, Ministry of Health, Singapore. 2021-03-18T08:54:01Z 2021-03-18T08:54:01Z 2020 Journal Article Bandeira, F., Goh, T., Setiawan, M., Yam, G. H. & Mehta, J. S. (2020). Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors. Stem Cell Research & Therapy, 11(1). https://dx.doi.org/10.1186/s13287-019-1533-1 1757-6512 0000-0002-8445-3669 https://hdl.handle.net/10356/146997 10.1186/s13287-019-1533-1 31900226 2-s2.0-85077479745 1 11 en NMRC/TCR/008-SERI/2013 JRNMRR163801 Stem Cell Research & Therapy © 2019 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Corneal Epithelium
Limbal Stem Cell Deficiency
spellingShingle Science::Biological sciences
Corneal Epithelium
Limbal Stem Cell Deficiency
Bandeira, Francisco
Goh, Tze-Wei
Setiawan, Melina
Yam, Gary Hin-Fai
Mehta, Jodhbir Singh
Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
description Background: Persistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET). Methods: STEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry. Tissue-engineered (TE) MET-Epi cells on fibrin gel were transplanted to corneal surface of the rat LSCD model caused by alkali injury. Epithelial healing, corneal edema, and haze grading, CE formation were assessed by fluorescein staining, slit lamp bio-microscopy, anterior segment optical coherence tomography, and immunohistochemistry. Results: CD73high/CD90high/CD105high/CD166high/CD14negative/CD31negativehuman ADSC underwent MET, giving viable epithelial-like progenitors expressingδNp63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-β4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epicells expressing cell junction proteins ZO1 and occludin. When transplanted onto rat corneal surface with LSCD-induced PED, TE-MET-Epi achieved more efficient epithelial healing, suppressed corneal edema, and opacities, when compared to corneas without treatment or transplanted with TE-ADSC. CE markers (CK3, 12, and CDH1) were expressed on TE-MET-Epi-transplanted corneas but not in other control groups. Conclusion: Human ADSC-derived epithelial-like cells, via MET, recovered the CE from PED associated with LSCD. ADSC can be a viable adult stem cell source for potential autologous epithelial cell-based therapy for corneal surface disorders.
author2 School of Materials Science and Engineering
author_facet School of Materials Science and Engineering
Bandeira, Francisco
Goh, Tze-Wei
Setiawan, Melina
Yam, Gary Hin-Fai
Mehta, Jodhbir Singh
format Article
author Bandeira, Francisco
Goh, Tze-Wei
Setiawan, Melina
Yam, Gary Hin-Fai
Mehta, Jodhbir Singh
author_sort Bandeira, Francisco
title Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
title_short Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
title_full Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
title_fullStr Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
title_full_unstemmed Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
title_sort cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
publishDate 2021
url https://hdl.handle.net/10356/146997
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