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Anti‐Angiogenic Factors of Tissue‐Engineered Oral Mucosal Epithelial Cell Sheets for Corneal Regeneration
Author(s) -
BardagGorce Fawzia,
Vilana Joan Oliva,
Wood Andrew,
Makalinao Andrew,
Pan Derek,
Sota Hiroyuki,
Niihara Yutaka
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.685.4
Subject(s) - regeneration (biology) , transplantation , wound healing , cell , epithelium , microbiology and biotechnology , cornea , angiogenesis , stem cell , matrix metalloproteinase , pathology , biology , cancer research , immunology , medicine , ophthalmology , surgery , biochemistry , genetics
Corneal regeneration by autologous oral mucosal epithelial cell sheet transplantation has been successfully performed in limbal stem cell deficiency (LSCD) patients. However, the molecular mechanism by which cell sheet grafting efficiently suppresses corneal vascularization, a major symptom of LSCD, is not fully understood. Here, we report the differential expression of pro‐ and anti‐angiogenic factors in cell sheets engineered from isolated rabbit oral mucosal epithelial cells, harvested on thermo‐responsive culture dish (UpCell®, CellSeed, Inc., Japan). A gene expression profiling‐directed study, followed by protein and histological analyses of cell sheets, showed a down‐regulation of pro‐angiogenic MMP‐3, and an up‐regulation of wound healing‐related proteins, MMP‐13 and collagen VIII. MMPs inhibitors, TIMP‐1 and TIMP‐3, were found to be expressed in cell sheets, thus reflecting a fine tuned balance between the pro‐ and anti‐angiogenic factors. These results indicated that tissue‐engineered cell sheets acquired a suppressive capability against corneal vascularization.