The road to generating transplantable organs: from blastocyst complementation to interspecies chimeras.

Growing human organs in animals sounds like something from the realm of science fiction, but it may one day become a reality through a technique known as interspecies blastocyst complementation. This technique, which was originally developed to study gene function in development, involves injecting donor pluripotent stem cells into an organogenesis-disabled host embryo, allowing the donor cells to compensate for missing organs or tissues. Although interspecies blastocyst complementation has been achieved between closely related species, such as mice and rats, the situation becomes much more difficult for species that are far apart on the evolutionary tree. This is presumably because of layers of xenogeneic barriers that are a result of divergent evolution. In this Review, we discuss the current status of blastocyst complementation approaches and, in light of recent progress, elaborate on the keys to success for interspecies blastocyst complementation and organ generation.

Growth Competition in Interspecies Chimeras: A New Paradigm for Blastocyst Complementation.

Blastocyst complementation represents a powerful technique for interspecies organogenesis but is limited by low chimerism due to developmental incompatibilities. In this issue of Cell Stem Cell,Nishimura et al. (2021) circumvent early developmental barriers by disabling Igf1r in host embryos, conferring donor cells with a growth advantage from mid-gestation onward.