• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2020 Fiscal Year Research-status Report

The development of human iPSC derived proliferative progenitors for the effectively massive production of liver organoid

Research Project

Project/Area Number 20K22946
Research InstitutionThe University of Tokyo

Principal Investigator

聶 運中  東京大学, 医科学研究所, 助教 (00831330)

Project Period (FY) 2020-09-11 – 2022-03-31
Keywordsliver organoid / hiPSC / progenitor / liver disease
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.

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.

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.

  • Research Products

    (2 results)

All 2020

All Presentation (1 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Presentation] Ex vivo evaluation of human hepatocyte plasticity2020

    • Author(s)
      Yun-Zhong Nie, Yun-Wen Zheng, Hideki Taniguchi
    • Organizer
      The International Society for Stem Cell Research
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 肝細胞の可塑性誘導法2020

    • Inventor(s)
      谷口英樹,聶運中,鄭允文
    • Industrial Property Rights Holder
      谷口英樹,聶運中,鄭允文
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      PCT/JP2020/36043

URL: 

Published: 2021-12-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi