title: Tumorigenesis in cells derived from induced pluripotent stem cells.
abstract: Induced pluripotent stem (iPS) cells are an attractive source for potential cell-replacement therapy. However, transplantation of differentiated products harbors the risk of teratoma formation, presenting a serious health risk. Thus, we characterized Nanog-expressing (undifferentiated) cells remaining after induction of differentiation by cytological examination. To induce differentiation of iPS cells, we generated embryoid bodies (EBs) derived from iPS cells carrying a Nanog–green fluorescent protein(GFP) reporter and then injected GFP-positive and GFP negative EBs into nude mice. GFP-positive EB transplantation resulted in the formation of immature teratoma grade 3, but no tumors were induced by GFP-negative EB. GFP positive cells revealed significantly lower cytoplasmic area and higher nucleus/cytoplasm ratio than those of GFP negative cells. Our results suggest that morphological analysis might be a useful method for distinguishing between tumorigenic and nontumorigenic iPS cells.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishimori
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yakushiji
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mori
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Setsuyo
authors.initials: S
authors.lastname: Ohno
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Miyake
authors.forename: Takuya
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Ueda
authors.forename: Eiji
authors.initials: E
authors.lastname: Ohno
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D058732:Embryoid Bodies / Q000166:cytology; D049452:Green Fluorescent Proteins; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013724:Teratoma / Q000209:etiology* / Q000473:pathology*
chemical_list: D049452:Green Fluorescent Proteins