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Improving iPSC Differentiation Using a Nanodot Platform.
Chiew, Men Yee; Wang, Erick; Lan, Kuan-Chun; Lin, Yan-Ren; Hsueh, Yu-Huan; Tu, Yuan-Kun; Liu, Chu-Feng; Chen, Po-Chun; Lu, Huai-En; Chen, Wen Liang.
Affiliation
  • Chiew MY; Center for Regenerative Medicine and Cellular Therapy, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan, ROC.
  • Wang E; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan, ROC.
  • Lan KC; Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan, ROC.
  • Lin YR; College of Biological Science and Technology Industrial Ph. D. Program, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan, ROC.
  • Hsueh YH; Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8397, Japan.
  • Tu YK; Department of Emergency and Critical Care Medicine, Changhua Christian Hospital, Changhua 500, Taiwan, ROC.
  • Liu CF; Department of Post Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan, ROC.
  • Chen PC; School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
  • Lu HE; School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
  • Chen WL; College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan, ROC.
ACS Appl Mater Interfaces ; 16(28): 36030-36046, 2024 Jul 17.
Article in En | MEDLINE | ID: mdl-38951110
ABSTRACT
Differentiation of induced pluripotent stem cells (iPSCs) is an extremely complex process that has proven difficult to study. In this research, we utilized nanotopography to elucidate details regarding iPSC differentiation by developing a nanodot platform consisting of nanodot arrays of increasing diameter. Subjecting iPSCs cultured on the nanodot platform to a cardiomyocyte (CM) differentiation protocol revealed several significant gene expression profiles that were associated with poor differentiation. The observed expression trends were used to select existing small-molecule drugs capable of modulating differentiation efficiency. BRD K98 was repurposed to inhibit CM differentiation, while iPSCs treated with NSC-663284, carmofur, and KPT-330 all exhibited significant increases in not only CM marker expression but also spontaneous beating, suggesting improved CM differentiation. In addition, quantitative polymerase chain reaction was performed to determine the gene regulation responsible for modulating differentiation efficiency. Multiple genes involved in extracellular matrix remodeling were correlated with a CM differentiation efficiency, while genes involved in the cell cycle exhibited contrasting expression trends that warrant further studies. The results suggest that expression profiles determined via short time-series expression miner analysis of nanodot-cultured iPSC differentiation can not only reveal drugs capable of enhancing differentiation efficiency but also highlight crucial sets of genes related to processes such as extracellular matrix remodeling and the cell cycle that can be targeted for further investigation. Our findings confirm that the nanodot platform can be used to reveal complex mechanisms behind iPSC differentiation and could be an indispensable tool for optimizing iPSC technology for clinical applications.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Differentiation / Myocytes, Cardiac / Induced Pluripotent Stem Cells Limits: Humans Language: En Journal: ACS Appl Mater Interfaces Journal subject: BIOTECNOLOGIA / ENGENHARIA BIOMEDICA Year: 2024 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cell Differentiation / Myocytes, Cardiac / Induced Pluripotent Stem Cells Limits: Humans Language: En Journal: ACS Appl Mater Interfaces Journal subject: BIOTECNOLOGIA / ENGENHARIA BIOMEDICA Year: 2024 Document type: Article Country of publication: United States