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Title: Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors
Authors: Bandeira, F.
Goh, T.-W.
Setiawan, M.
Yam, G.H.-F. 
Mehta, J.S. 
Keywords: Adipose mesenchymal stem cells
Corneal epithelium
Epithelial reconstruction
Limbal stem cell deficiency
Mesenchymal-epithelial transition
Issue Date: 2020
Publisher: BioMed Central Ltd
Citation: Bandeira, F., Goh, T.-W., Setiawan, M., Yam, G.H.-F., Mehta, J.S. (2020). Cellular therapy of corneal epithelial defect by adipose mesenchymal stem cell-derived epithelial progenitors. Stem Cell Research and Therapy 11 (1) : 191533. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: 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-? 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/CD31negative human ADSC underwent MET, giving viable epithelial-like progenitors expressing ?Np63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-?4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epi cells 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. © 2019 The Author(s).
Source Title: Stem Cell Research and Therapy
ISSN: 1757-6512
DOI: 10.1186/s13287-019-1533-1
Rights: Attribution 4.0 International
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