TY - JOUR
T1 - Nanotopography Promotes Pancreatic Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells
AU - Kim, Jong Hyun
AU - Kim, Hyung Woo
AU - Cha, Kyoung Je
AU - Han, Jiyou
AU - Jang, Yu Jin
AU - Kim, Dong Sung
AU - Kim, Jong Hoon
N1 - Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2014R1A2A1A01006527, 2011-0030075) and Industrial Core Technology Development Program, (Project No. 10041913) funded by the Ministry of Trade, Industry and Energy (MI, Republic of Korea). We appreciate the technical help of Dr. Jiwon Lim of the Department of Mechanical Engineering in POSTECH for measuring protein adsorption.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/3/22
Y1 - 2016/3/22
N2 - 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.
AB - 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.
KW - human embryonic stem cells
KW - induced pluripotent stem cells
KW - nanoinjection molding
KW - pancreatic differentiation
KW - polystyrene nanopore surfaces
UR - http://www.scopus.com/inward/record.url?scp=84961875440&partnerID=8YFLogxK
U2 - 10.1021/acsnano.5b06985
DO - 10.1021/acsnano.5b06985
M3 - Article
C2 - 26900863
AN - SCOPUS:84961875440
VL - 10
SP - 3342
EP - 3355
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 3
ER -