| Project/Area Number |
23K25188
|
|---|
| Project/Area Number (Other) |
22H03934 (2022-2023)
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Multi-year Fund (2024)
Single-year Grants (2022-2023) |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 90110:Biomedical engineering-related
|
|---|
| Research Institution | The University of Tokyo |
|---|
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)
|
|---|
| 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)
DANOY MATHIEU 東京大学, 大学院工学系研究科(工学部), 助教 (90882621)
|
|---|
| Project Period (FY) |
2022-04-01 – 2025-03-31
|
| Project Status |
Granted (Fiscal Year 2024)
|
| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2024: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2023: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2022: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
|
|---|
| Keywords | liver organ on chip / stem cells / fibrosis / fatty acids / hiPSCS / hepatic disorders / liver disease model / organ on chip / liver / liver on chip / pluripotent stem cells / disease model / multi cellular cultures / MicroPhysiologicalSystem / Liver / iPSCs |
|---|
| Outline of Research at the Start |
The purpose of the research is to develop tri culture model of liver derived human induced pluripotent stem cells to build a hepatic tissue. Then we proposed to investigate liver disorder.
We wish to induce a hepatic fibrosis like disorder using physio pathological sequence due to free fatty acids exposure within organ on chip technology. Finally we aim at testing an anti fibrotic treatment as one exemple of one therapeutical strategy.
|
| 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.
|
| 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.
|
| 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
|
