2020 Fiscal Year Research-status Report
The development of human iPSC derived proliferative progenitors for the effectively massive production of liver organoid
| Project/Area Number |
20K22946
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| Research Institution | The University of Tokyo |
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Principal Investigator |
聶 運中 東京大学, 医科学研究所, 助教 (00831330)
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Keywords | liver organoid / hiPSC / progenitor / liver disease |
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| Outline of Annual Research Achievements |
The development of new transplantable human livers is urgently needed due to the persistent profound shortage of transplantable donors to treat end-stage liver diseases. In this project, we aim to develop an efficiently massive production system of LOs based on hiPSC derived proliferative progenitors, including hepatoblasts, fetal hepatic stellate cells, and endothelial progenitors. Next, we will evaluate the function of the progenitors derived LOs in vitro and in vivo and investigate their usefulness for the treatment of liver diseases. Last year, we established protocols for the differentiation of hepatoblast, fetal hepatic stellate cell, and endothelial progenitors from hiPSCs. Moreover, we optimized the culture conditions that could help maintain the proliferation of these hiPSC derived progenitor cells.
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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
In the last year, we developed protocols to generate hepatoblast, fetal hepatic stellate cells, and endothelial progenitor cells from hiPSCs and identified the cellular characteristics of these progenitor cells. Moreover, we optimized the conditions for maintaining the proliferative capacity of these progenitors. In the optimized combination of cytokines and small-molecule compounds, these progenitors could also maintain the cellular characteristics during passages. The successful establishment of these proliferative progenitors makes it possible to develop an efficiently massive production system of liver organoids. Therefore, this research is expected to progress smoothly.
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| Strategy for Future Research Activity |
To ensure the safety of the proliferative progenitors in further application, we will subcutaneously transplant these proliferative progenitors into immunodeficiency mice to detect the tumorigenicity. Moreover, we will evaluate the functions of progenitors-derived LOs with our advanced organoid culture technologies and compare the functional differentiation between our developed LO and the progenitors-derived LO. Finally, we try to transplant the progenitors derived LO into liver disease models and investigate this LO's usefulness for disease treatment.
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Research Products
(2 results)
