2023 Fiscal Year Annual Research Report
Liver fibrosis investigation using iPSCs hepatic derived organ on chip
| Project/Area Number |
22H03934
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
LECLERC Eric 東京大学, 大学院工学系研究科(工学部), 外国人客員研究員 (30759436)
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| Co-Investigator(Kenkyū-buntansha) |
酒井 康行 東京大学, 大学院工学系研究科(工学部), 教授 (00235128)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Keywords | liver organ on chip / hiPSCS / hepatic disorders |
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| Outline of Annual Research Achievements |
In 2023/204 we have published a first paper describing the results of a tri culture of hepatocytes like cells (HLCs), liver sinusoidal like cells (LSECs) and hepatic stellate like cells (HSCs) derived from human induced pluripotent stem cells and cultivated in biochips. Then, we have produced new batch of HLCs, LSECs and HSCs to improve this biochip tri culture and to generate disease models. We submitted a paper in which we investigate palmitic acid toxic to HLCs to move toward fatty acid induced fibrosis. Finally, we performed HLCs, LSECs, HSCs new tri culture biochips exposed to fatty acids to generate a fibrosis like disease.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We have repeated the HLCs, LSECs and HSCs differentiation and their tri culture in biochips. We found that the time for hepatic maturation was longer than expected leading to perform long term culture up to 4 weeks in biochips (rather than 2 weeks initially). We also found that inoculation step in biochip is critical and need to be refined. This contributed to increase the experimental culture time and to modify the protocol from our first tri culture publication. TGF beta induced disease data were also analyzed and we now going to more physiological induction of the disease by using fatty acids induction. Furthermore, the single cell sequencing post processing is time consuming and is still under analysis.
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| Strategy for Future Research Activity |
In the next fiscal year, we are planning to
- continue the post processing and analysis of the single cells sequencing data of induced fibrosis by fatty acids inside biochip tri cultures
- to repeat this tri culture biochips experiments to generate additional data of fibrosis like situation induced by fatty acid treatment(for additional assays and immunostaining).
- to est anti fibrotic drugs such as emodine. Emodine can inhibit the TGF activation and reduce the inflammation (the experiment of tri culture in biochips, exposed to fatty acid demonstrate potential TGF pathway activation).
- Make the data analysis and write publications
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