| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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