2021 Fiscal Year Annual Research Report
疾患スクリーニングのための生理的肝臓モデル培養系の構築
| Project/Area Number |
20K22491
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| Research Institution | The University of Tokyo |
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Principal Investigator |
DANOY MATHIEU 東京大学, 大学院工学系研究科(工学部), 助教 (90882621)
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Keywords | hiPSCs / HSCs / Liver / Disease / LSECs / Hepatocytes / Inflammation / Coculture |
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| Outline of Annual Research Achievements |
The purpose of this project is the establishment of a physiologically-relevant liver model compatible with drug screening technologies. In that regard, several cellular components such as hepatocytes, Hepatic Stellate Cells (HSCs), and Liver Sinusoidal Endothelial Cells (LSECs) among other, have to be investigated. hiPSCs-derived hepatocyte and LSEC models were previously established in our group, so the focus was set on HSCs. Especially, HSCs tend to spontaneously activate in vitro which causes to model disease rather than physiology. In that regard, the physical environment of hiPSCs-derived HSCs as well as its composition was varied via the use of different extracellular matrixes. By doing so, optimized conditions in which quiescence could be preserved to a certain extent were found. In addition, intensive work on reproducibility of the differentiation of HSCs from hiPSCs was performed and the response of the cells to inflammatory cytokines was also studied. Coculture of the previously cited hepatic cells was also performed in PDMS microfluidic devices and results are currently being analyzed. Results from this project were presented in national conferences and manuscripts are also in preparation for submission. Papers related to this topic were also published in peer-reviewed journals during the project.
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