Reprogramming oral epithelial keratinocytes into a pluripotent phenotype for tissue regeneration

Objectives: We set out to reprogram adult somatic oral epithelial keratinocytes into pluripotent cells for regenerative dentistry. Setting and Sample population: Immortalized murine oral keratinocyte cell (IMOK) line raised from adult mouse mucosa were cultured in vitro in our studies. Materials and Methods: Adult murine oral epithelial keratinocytes were chronically treated with TGF-β1 in vitro, and the expression of Oct4, Nanog, Sox2 and Nestin, as well as specific homeobox Gata and Pax gene family members were investigated. Results: We documented the induction of stem factors linked with pluripotency and/or the maintenance and regulation of stem-cell self-renewal in oral epithelial keratinocytes by TGFβ1. Moreover, we discovered that this TGF-β1-induced increase in Oct4, Nanog, Sox2 and Nestin was inhibited by SB431542, suggesting that TGF-β1 signals via the TGF-βRI receptor to induce pluripotency and stemness. Conclusions: Adult oral epithelial keratinocytes treated chronically with TGF-β1 acquired phenotypic characteristics consistent with pluripotent stem cells, highlighting the facileness of reprogramming adult oral keratinocytes into an unlimited supply of pluripotent stem cells.