Stem Cells and Interspecies Chimeras

The generation of human organs in animals through hPSC-based interspecies chimeras and blastocyst complementation has emerged as a transformative approach for regenerative medicine. Despite its promise, efficient human cell contribution remains a major challenge due to developmental incompatibilities between species, including differences in signaling pathways, cell competition, and cell adhesion. These barriers limit the survival and developmental potential of human cells within animal embryos, preventing the formation of functional humanized organs. In this presentation, I will highlight our laboratory's efforts to identify and overcome these barriers using genetic engineering and synthetic biology approaches. Our findings reveal key mechanisms that govern interspecies cell integration and establish new strategies for enhancing human chimerism, bringing the field closer to the goal of generating transplantable human tissues and organs in animal hosts.