Could E-cadherin overexpression promote epithelial differentiation of human adipose-derived stem cells by mediating mesenchymal-to-epithelial transition?

Abstract

After skin injury, one of the major components of the healing process is wound re-epithelialization, which is driven by residual epithelial stem cells from skin appendages. However, the re-epithelialization process is vulnerable to severe trauma due to irreversible damage to the skin appendages. Engineering a functionalized epithelium using pluripotent stem cells from other tissue sources could provide an extraordinary skin substitute that could rapidly close a wound while reducing secondary damage to the skin. Human adipose-derived stem cells (hASCs) are widely distributed in the subcutaneous tissue and can theoretically differentiate into epithelial lineage cells. However, a definite and effective induction protocol has not yet been developed, and thus epithelial phenotype establishment in hASCs remains difficult. In particular, hASCs are unable to produce the key trigger protein E-cadherin, which is required for epithelial transition; therefore, we hypothesized that the stable overexpression of E-cadherin in hASCs could induce the epithelial phenotype in hASCs via the mesenchymal-to-epithelial transition (MET), making hASCs qualified candidates for wound re-epithelialization and skin tissue engineering. The achievement of the N- to E-cadherin switch in hASCs might induce epithelialized characteristics (such as epithelial cell junctions, apicobasal polarity, cytokeratin production, and loss of original mesenchymal features) in hASCs, which exhibit functionality similar to that of keratinocytes. Combining epithelialized hASCs with inductive scaffolds could allow them to be applied in epithelial tissue engineering, thus providing a sufficient source of skin substitutes to treat refractory wounds. Moreover, epithelialized hASCs could be the subject of future research exploring the in-depth molecular biological mechanism of MET mediated by E-cadherin.