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Table 3 Recently suggested phenotypic markers of healthy and transformed CECs that can identify the endothelial phenotype

From: Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review

Cell marker (gene) Molecular family Function Ref
Healthy CEC phenotype
Cadherin-2/N-cadherin (CDH2) Transmembrane protein Regulates contact inhibition, proliferation, and EndMT. Proteomic analysis confirmed its exclusive expression in ex vivo CECs [18, 33]
CD56/neural cell adhesion molecule 1 (NCAM1) Glycoprotein Cell adhesion, cell interactions, migration, embryogenesis; a functional marker of the ability of CECs to form tight junctions. Proteomic analysis found NCAM1 expression also in ex vivo corneal stromal keratocytes [18, 31, 108]
CD98/large neutral amino acid transporter
(SLC3A2 + SLC7A5)
Heterodimeric transmembrane glycoprotein Sodium-independent amino acid antiport, transportation of non-amino acid substrates across the cell membrane. Proteomic analysis found SLC3A2 gene expression also in ex vivo corneal stromal keratocytes and epithelial cells [18, 129]
Immunoglobulin receptor T-cell activation and proliferation maintain tissue architecture, mediate homotypic interactions with other ALCAMs. Proteomic study confirmed its specificity to ex vivo CECs [18, 130]
CD340/receptor tyrosine protein kinase erbB-2 (ERBB2) Cell membrane tyrosine kinase Binds to other ligand-bound EGF receptors, stimulating cytoplasmic kinase activation and transphosphorylation. Proteomic analysis found ERBB2 gene expression also in ex vivo corneal stromal keratocytes and epithelial cells [18, 129]
Sodium bicarbonate transporter-like protein 11 (SLC4A11) Transmembrane protein carrier Cotransporter that is highly expressed in in vivo and in vitro CE and is critical for CEC function. Its expression in CECs decreases with the increasing in vitro passages and also at high mitogenic conditions. Proteomic study found its expression mainly in ex vivo CECs, but small expression was also in ex vivo keratocytes [18, 109]
Transmembrane Protein 178A
Transmembrane protein A negative regulator of osteoclast differentiation in basal and inflammatory conditions. A specific cell surface marker expressed in early passages of human CECs (donors: ˂ 40 years old) [15, 18]
Transformed (fibroblastic) CEC phenotype
CD24 antigen (CD24) Sialoglycoprotein Cell adhesion molecule that may have a pivotal role in the differentiation of different cell types. CD24+ subpopulations of cultured human CECs contain chromosomal aberrations (trisomy) [131]
CD44 antigen (CD44) Glycoprotein Receptor binding ECM components important for cell–cell interactions, cell migration, and maintenance of stem cell features. Expressed in ex vivo corneal epithelial cells and keratocytes; its expression in in vitro cultured CECs increases with the increasing passages. CD44+ subpopulations of cultured human CECs contain chromosomal aberrations (trisomy) [18, 131]
CD105 antigen/endoglin (ENG) Glycoprotein Regulates angiogenesis; TGF-β coreceptor involved in the TGF-β/BMP signaling cascade. According to the proteomic study, it is also present in ex vivo CECs [18, 131]
CD109 antigen (CD109) Glycoprotein Binds and negatively regulates TGF-β signaling. Increased expression in cultured human CECs with modified (non-canonical) morphology and EndMT cells [108]
CD133 antigen/prominin 1 (PROM1) Transmembrane glycoprotein Cell differentiation, proliferation, and apoptosis; bind cholesterol, cadherin, and actinin. The flow cytometry analysis of surface markers identified CD166+/CD133/CD105/CD44/CD26/CD24 subpopulations of cultured human CECs as the most suitable cells for Tx [26]