An organism composed of two or more genetically distinct cells is called a chimera.A group of Professor Hiromitsu Nakauchi of the Institute of Medical Science, the University of Tokyo, created a chimera between humans and heterologous animals using a technique called blastocyst complementation, and created human organs in the heterogeneous animals for transplantation treatment. It is said that it aims to be used for.
So far, we have succeeded in producing a pancreas derived from rat pluripotent stem cells in a pancreas-deficient mouse, but we have not succeeded between animal species with a genetic distance.One reason for this is that in order to produce an organ derived from a donor cell in a heterologous body, a certain level of donor cell chimerism (donor chimerism: the ratio of donor cells in the chimera) is required, while high donor chimerism is There is a problem that it hinders the early development of heterologous chimeric embryos and induces embryonic lethality.
With the aim of developing a method for increasing donor chimerism without interfering with early development, in this study, we conducted an insulin-like growth factor 1 receptor that plays an important role in cell proliferation and differentiation from late lung development in host cells of chimeric embryos. By deleting (Igf1r), we attempted to induce a microenvironment (cell competition niche) in which donor cells proliferate and differentiate predominantly.As a result, it was found that donor chimerism is constant during development in normal chimeric individuals, whereas donor chimerism increases with development in cell competition niches, and in adults, organs composed mostly of donor cells are induced. rice field.Similar results were obtained in both mouse allogeneic chimeric embryos and mouse and rat heterologous chimeric embryos, and it was also found that donor chimerism increased from the late embryonic development stage, which did not interfere with the early development of the heterologous chimeric embryos.
By developing a method that can realize the production of heterogeneous chimeras with high donor chimerism, which was difficult until now, the application development to human organ regeneration research in heterogeneous animals will be challenged by Professor Nakauchi and others in the future. There is expected.
Paper information:[Cell Stem Cell] Generation of Functional Organs Using a Cell Competitive Niche in Intra-and Inter-species Rodent Chimeras
