Pluripotent stem cell-derived organogenesis in the rat model system

Rats make an excellent model system for studying xenotransplantation since, like mice pluripotent stem cell lines, such as embryonic stem cells and induced pluripotent stem cells as well as gene knock-outs are also available for rats, besides rats have larger organs. The emergence of new genome-editing tools combined with stem cell technology, has revolutionized biomedical research including the field of regenerative medicine. The aim of this manuscript is to provide an overview of the recent progresses in stem cell-derived organ regeneration involving "gene knock-out" and "blastocyst complementation" in the rat model system. Knocking-out Pdx1, Foxn1, and Sall1 genes have successfully generated rat models lacking the pancreas, thymus, and kidney, respectively. When allogeneic (rat) or xenogeneic (mouse) pluripotent stem cells were microinjected into blastocyst-stage rat embryos that had been designed to carry a suitable organogenetic niche, devoid of specific organs, the complemented blastocysts were able to develop to full-term chimeric rat offspring containing stem cell-derived functional organs in their respective niches. Thus, organs with a tridimensional structure can be generated with pluripotent stem cells in vivo, accelerating regenerative medical research, which is crucial for organ-based transplantation therapies. However, to address ethical concerns, public consent after informed discussions is essential before production of human organs within domestic animals.