title: Self-renewal of embryonic stem cells through culture on nanopattern polydimethylsiloxane substrate.
abstract: Embryonic stem (ES) cells can undergo continual proliferation and differentiation into cells of all somatic cell lineages in vitro; they are an unlimited cell source for regenerative medicine. However, techniques for maintaining undifferentiated ES cells are often inefficient and result in heterogeneous cell populations. Here, we determined effects of nanopattern polydimethylsiloxane (PDMS) as a culture substrate in promoting the self-renewal of mouse ES (mES) cells, compared to commercial plastic culture dishes. After many passages, mES cells efficiently maintained their undifferentiated state on nanopattern PDMS, but randomly differentiated on commercial plastic culture dishes, as indicated by partially altered morphologies and decreases in alkaline phosphatase activity and stage-specific expression of embryonic antigen-1. Under nanopattern PDMS conditions, we found increased activities of STAT3 and Akt, important proteins involved in maintaining the self-renewal of mES cells. The substrate-cell interactions also enhanced leukemia inhibitory factor (LIF)-downstream signaling and inhibited spontaneous differentiation, concomitant with reduced focal adhesion kinase (FAK) signaling. This reduction in FAK signaling was shown to be important for promoting mES cell self-renewal. Thus, our data demonstrates that nanopattern PDMS contributes to maintaining the self-renewal of mES cells and may be applicable in the large-scale production of homogeneously undifferentiated mES cells.
authors.affiliation: Department of Animal Biotechnology (BK21), Animal Resources Research Center and SMART-IABS, Konkuk University, Seoul 143-702, Republic of Korea.
authors.forename: Kilsoo
authors.initials: K
authors.lastname: Jeon
authors.forename: Hyun-Jik
authors.initials: HJ
authors.lastname: Oh
authors.forename: Hyejin
authors.initials: H
authors.lastname: Lim
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Duk Hyun
authors.initials: DH
authors.lastname: Lee
authors.forename: Eung-Ryoung
authors.initials: ER
authors.lastname: Lee
authors.forename: Bae Ho
authors.initials: BH
authors.lastname: Park
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004129:Dimethylpolysiloxanes / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D013499:Surface Properties / Q000187:drug effects
chemical_list: D004129:Dimethylpolysiloxanes; D053605:Leukemia Inhibitory Factor; C013830:baysilon; D051416:Focal Adhesion Protein-Tyrosine Kinases