Generation of Rat Panc c m u e

lo es U pCurrent stem cell therapy mainly targets diseases that can be treated by cell replacement, such as Parkinson’s disease or dia-by early embryonic interactions of mesenchyme and epithelium (Slack, 1995). Pdx1 (pancreatic and duodenal homeobox1) is a Hox-type transcription factor that plays a critical role in pancre-betes mellitus. One of the ultimate goals of regenerative medi-cine, however, is to grow organs using the patient’s own stem atic development and b cell maturation. Homozygous deficiency of Pdx1 in the mouse results in death soon after birth due toPdx1 (pancreatogenesis-disabled) mouse blasto-cysts developmentally compensated vacancy of the pancreatic ‘‘developmental niche,’ ’ generating almost entirely PSC-derived pancreas. To examine the potential for xenogenic approaches in blastocyst complementation,we injectedmouseor ratPSCs into rat or mouse blastocysts, respectively, generating interspecific chimeras and thus confirming that PSCs can contribute to xenogenic development between mouse and rat. The development of these mouse/rat chimeras was primarily influenced by host blastocyst and/or foster mother, evident by body size and species-specific organogenesis. We further injected rat wild-type PSCs into Pdx1/ mouse blastocysts, generating normally functioning rat pancreas in Pdx1/ mice. These data constitute proof of principle for interspecific blastocyst comple-mentationand for generation in vivooforgansderived from donor PSCs using a xenogenic environment