Jong Hyun Kim†§, Hyung Woo Kim‡§, Kyoung Je Cha‡⊥, Jiyou Han†, Yu Jin Jang†, Dong Sung Kim*‡, and Jong-Hoon Kim*†
† 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
‡ Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-gu, Pohang, Gyeongbuk 37673, Korea
⊥Author Present Address
Ultimate Manufacturing Technology Group, Korea Institute of Industrial Technology (KITECH), Techno Sunwan-ro Yuga-myeon Dalseong-gun, Deagu 711-880, Korea.
J.H.K. and H.W.K. contributed equally to this work as first authors.
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.
Keywords: polystyrene nanopore surfaces; nanoinjection molding; human embryonic stem cells; induced pluripotent stem cells; pancreatic differentiation