title: Nanotopography Promotes Pancreatic Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells.
abstract: Although previous studies suggest that nanotopographical features influence properties and behaviors of stem cells, only a few studies have attempted to derive clinically useful somatic cells from human pluripotent stem cells using nanopatterned surfaces. In the present study, we report that polystyrene nanopore-patterned surfaces significantly promote the pancreatic differentiation of human embryonic and induced pluripotent stem cells. We compared different diameters of nanopores and showed that 200 nm nanopore-patterned surfaces highly upregulated the expression of PDX1, a critical transcription factor for pancreatic development, leading to an approximately 3-fold increase in the percentage of differentiating PDX1(+) pancreatic progenitors compared with control flat surfaces. Furthermore, in the presence of biochemical factors, 200 nm nanopore-patterned surfaces profoundly enhanced the derivation of pancreatic endocrine cells producing insulin, glucagon, or somatostatin. We also demonstrate that nanopore-patterned surface-induced upregulation of PDX1 is associated with downregulation of TAZ, suggesting the potential role of TAZ in nanopore-patterned surface-mediated mechanotransduction. Our study suggests that appropriate cytokine treatments combined with nanotopographical stimulation could be a powerful tool for deriving a high purity of desired cells from human pluripotent stem cells.
authors.affiliation: Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Science Campus, Korea University , 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea.
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-Ro, Nam-gu, Pohang, Gyeongbuk 37673, Korea.
authors.forename: Hyung Woo
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-Ro, Nam-gu, Pohang, Gyeongbuk 37673, Korea.
authors.forename: Kyoung Je
authors.initials: KJ
authors.lastname: Cha
authors.affiliation: Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Science Campus, Korea University , 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea.
authors.forename: Jiyou
authors.initials: J
authors.lastname: Han
authors.affiliation: Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Science Campus, Korea University , 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jang
authors.affiliation: Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH) , 77 Cheongam-Ro, Nam-gu, Pohang, Gyeongbuk 37673, Korea.
authors.forename: Dong Sung
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Science Campus, Korea University , 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D018398:Homeodomain Proteins / Q000032:analysis; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D040542:Mechanotransduction, Cellular; D058608:Nanopores / Q000648:ultrastructure*; D010179:Pancreas / Q000166:cytology*; D011137:Polystyrenes / Q000737:chemistry*; D013499:Surface Properties; D054457:Tissue Scaffolds / Q000737:chemistry*; D015534:Trans-Activators / Q000032:analysis
chemical_list: D018398:Homeodomain Proteins; D011137:Polystyrenes; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein
keywords: human embryonic stem cells; induced pluripotent stem cells; nanoinjection molding; pancreatic differentiation; polystyrene nanopore surfaces