title: Induction of pluripotent stem cells from human third molar mesenchymal stromal cells.
abstract: The expression of four transcription factors (OCT3/4, SOX2, KLF4, and MYC) can reprogram mouse as well as human somatic cells to induced pluripotent stem (iPS) cells. We generated iPS cells from mesenchymal stromal cells (MSCs) derived from human third molars (wisdom teeth) by retroviral transduction of OCT3/4, SOX2, and KLF4 without MYC, which is considered as oncogene. Interestingly, some of the clonally expanded MSCs could be used for iPS cell generation with 30-100-fold higher efficiency when compared with that of other clonally expanded MSCs and human dermal fibroblasts. Global gene expression profiles demonstrated some up-regulated genes regarding DNA repair/histone conformational change in the efficient clones, suggesting that the processes of chromatin remodeling have important roles in the cascade of iPS cells generation. The generated iPS cells resembled human embryonic stem (ES) cells in many aspects, including morphology, ES marker expression, global gene expression, epigenetic states, and the ability to differentiate into the three germ layers in vitro and in vivo. Because human third molars are discarded as clinical waste, our data indicate that clonally expanded MSCs derived from human third molars are a valuable cell source for the generation of iPS cells.
authors.affiliation: Tissue Engineering Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology, Hyogo 661-0974, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Oda
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Hiroe
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Mika
authors.initials: M
authors.lastname: Tadokoro
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Katsube
authors.forename: Mari
authors.initials: M
authors.lastname: Sasao
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kubo
authors.forename: Koji
authors.initials: K
authors.lastname: Hattori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Horimoto
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yuba
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohgushi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D007621:Karyotyping; D000090062:Kruppel-Like Factor 4; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D014070:Tooth / Q000166:cytology*