title: Targeted organ generation using Mixl1-inducible mouse pluripotent stem cells in blastocyst complementation.
abstract: Generation of functional organs from patients' own cells is one of the ultimate goals of regenerative medicine. As a novel approach to creation of organs from pluripotent stem cells (PSCs), we employed blastocyst complementation in organogenesis-disabled animals and successfully generated PSC-derived pancreas and kidneys. Blastocyst complementation, which exploits the capacity of PSCs to participate in forming chimeras, does not, however, exclude contribution of PSCs to the development of tissues-including neural cells or germ cells-other than those specifically targeted by disabling of organogenesis. This fact provokes ethical controversy if human PSCs are to be used. In this study, we demonstrated that forced expression of Mix-like protein 1 (encoded by Mixl1) can be used to guide contribution of mouse embryonic stem cells to endodermal organs after blastocyst injection. We then succeeded in applying this method to generate functional pancreas in pancreatogenesis-disabled Pdx1 knockout mice using a newly developed tetraploid-based organ-complementation method. These findings hold promise for targeted organ generation from patients' own PSCs in livestock animals.
authors.affiliation: 1 Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo , Tokyo, Japan .
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Megumi
authors.initials: M
authors.lastname: Kato-Itoh
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis; D010179:Pancreas / Q000166:cytology / Q000196:embryology*; D015534:Trans-Activators / Q000096:biosynthesis
chemical_list: D018398:Homeodomain Proteins; C464781:Mixl1 protein, mouse; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein