title: Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells.
abstract: BACKGROUND
  Application of induced pluripotent stem (iPS) cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, and tailor-made medicine. However, in order to apply iPS cells to mitotic tissue, induction of tissue stem cells that give rise to progeny of the target organ is required.
  
  
  RESULTS
  We induced stratified epithelial cells from mouse iPS cells by co-culture with PA6 feeder cells (SDIA-method) with use of BMP4. Clusters of cells positive for the differentiation markers KRT1 or KRT12 were observed in KRT14-positive colonies. We successfully cloned KRT14 and p63 double-positive stratified epithelial progenitor cells from iPS-derived epithelial cells, which formed stratified epithelial sheets consisting of five- to six-polarized epithelial cells in vitro. When these clonal cells were cultured on denuded mouse corneas, a robust stratified epithelial layer was observed with physiological cell polarity including high levels of E-cadherin, p63 and K15 expression in the basal layer and ZO-1 in the superficial layer, recapitulating the apico-basal polarity of the epithelium in vivo.
  
  
  CONCLUSIONS
  These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can be cloned from iPS cells in order to produce polarized multilayer epithelial cell sheets.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yoshida
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yasuda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Miyashita
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Shigeto
authors.initials: S
authors.lastname: Shimmura
mesh_terms: D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003315:Cornea / Q000166:cytology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D023822:Tissue Engineering
chemical_list: D055415:Bone Morphogenetic Protein 4