― We postulated that an “organ niche” exists in a developing animal and that this niche was empty when development of an organ is genetical ly disabled. This organ niche should be compensated developmentally by blastocyst complementation using wild-type pluripotent stem cells (PSCs). We showed that in Pdx-1 deficient mice, inter-species blastocyst complementation with rat PSCs can create functional rat pancreata (Kobayashi et al. Cell. 2010). Although the resulting pancreata, made of rat PSC-derived cells, were functional they were of mouse size, making them insufficient for isolating the number of islets needed to treat diabetes in a rat model. We performed the reverse experiment, injecting mouse PSCs into Pdx-1 deficient rat blastocysts. The generated pancreata were composed of mouse PSCderived cells but were of rat size. Islets prepared from