The research group of Professor Takanori Takebe of Tokyo Medical and Dental University, in collaboration with Cincinnati Children's Hospital, was the first in the world to continue from human iPS cells by mimicking the process of liver, gall bladder, and pancreatic development in the womb. We have established a technology to simultaneously generate multiple (liver, gall bladder, pancreas) organs.Furthermore, we succeeded in reproducing in vitro a genetic disease that causes abnormalities in the formation of multiple organs.
In recent years, attention has been focused on attempts to artificially create specific organs from immature stem cells such as human iPS cells.However, induction of only a specific organ (single organ) does not reproduce the connection between multiple adjacent organs.For this reason, there have been serious unsolved problems such as insufficient or sustained organ function of interest.
In this study, we focused on the boundary region (boundary) of the precursor tissue called the foregut and midgut that occurs in the early stage of development and the cell-cell interaction of the surrounding cells, and attempted to reproduce them.First, the foregut and midgut tissues are separately induced from human iPS cells.Next, when they were connected to create a foregut-midgut boundary (boundary), progenitor cells of the liver, bile duct, and pancreas were spontaneously induced from the boundary region.
Furthermore, it was found that the appearance of these hepatic, biliary, and pancreatic progenitor cells requires complex cell-cell interactions through the exchange of molecules such as retinoic acid signals.Furthermore, by optimizing the culture method of the obtained tissue, liver, gall bladder, and pancreatic tissue are generated from the progenitor cells induced in vitro by a special three-dimensional culture for a long period of time while maintaining the continuity. I succeeded in making it.
From the results of this research, it is expected that organ creation technology based on a completely new concept will spread in the future, from single organ regeneration to multi-organ batch creation.
Paper information:[Nature] Modeling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary
