Histological analysis of epithelial stem cells during induced pluripotent stem cell-derived teratoma development

Abstract

ObjectiveInduced pluripotent stem (iPS) cells can differentiate into a variety of cell types and can form teratomas when transplanted in vivo. The purpose of the present study was to investigate the developmental processes and features of epithelial tissues, and the existence of epithelial stem/progenitor cells in iPS cell-derived teratomas. Materials and methodsiPS cell-derived teratomas formed by subcutaneous injection into immuno-deficient mice were extracted at 7-day intervals up to 21 day interval. Paraffin-embedded tissue sections were evaluated by H&E staining and immunohistochemistry for specific markers of three germ layer cell types and epithelial stem cells in oral tissues. ResultsDuring iPS cell-derived teratoma development, ectodermal cells emerged first, followed by the appearance of mesodermal and endodermal cells. The teratomas contained various types of epithelia, including epithelial masses, pseudostratified epithelium, simple epithelium and stratified epithelium. As teratoma development progressed, the epithelia matured. p63 and K14 were strongly expressed in epithelial masses and in the basal layer of pseudostratified and stratified epithelium. CD49f was expressed in all types of epithelia observed, and intense expression was observed in both the basal layer and luminal surface of pseudostratified and stratified epithelium. ConclusionsiPS cell-derived teratoma is a useful model for study of epithelial development, and it may provide significant information regarding oral epithelial tissue regeneration.