A research group led by Associate Professor Takanori Takebe and Professor Hideki Taniguchi of Yokohama City University has developed a method for mass-producing human mini-livers (iPSC liver buds) from iPS cells under an industry-academia collaboration system with multiple companies. succeeded in.
So far, a research group at Yokohama City University has established an epoch-making basic technology to create a liver primordium (mini-liver) with a vascular network from three different types of cells using human iPS cells.However, there were various problems such as mass production of mini-liver and stable method.
Traditionally, the cells required to make a human mini-liver are separated from the umbilical cord and bone marrow obtained during labor.However, from the viewpoint of standardization and expandability of the manufacturing process, we will investigate the induction method from human iPS cells (for research), and it is optimal to produce vascular progenitor cells and mesenchymal progenitor cells in addition to liver progenitor cells. Method was established.
As a result, it was confirmed that differentiation induction was possible with high efficiency, and when an attempt was made to produce a human mini-liver from the obtained cells, a three-dimensional human mini-liver was successfully produced.It was shown that the high function is stably shown as compared with the conventional method.
Next, with the aim of establishing a mass manufacturing process, in collaboration with Kuraray Co., Ltd., we developed a new culture equipment capable of manufacturing 0.1 mini-livers (0.2 to 2 mm) on a culture plate.We have also developed a culture operation technology that can obtain a mini-liver with even higher quality and homogeneity.Mass-produced mini-liver demonstrated that transplantation significantly improved the survival of immunocompromised mice developing severe liver disease.
Currently, the number of patients waiting for liver transplantation is more than 2 a year, and if regenerative medicine with this developed technology can be realized, it is expected that many patients will be rescued.In the future, it aims at clinical research aimed at evaluating the safety of human mini-liver transplantation.
Paper information:[Cell Reports] Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells