title: Interspecies organogenesis generates autologous functional islets.
abstract: Islet transplantation is an established therapy for diabetes. We have previously shown that rat pancreata can be created from rat pluripotent stem cells (PSCs) in mice through interspecies blastocyst complementation. Although they were functional and composed of rat-derived cells, the resulting pancreata were of mouse size, rendering them insufficient for isolating the numbers of islets required to treat diabetes in a rat model. Here, by performing the reverse experiment, injecting mouse PSCs into Pdx-1-deficient rat blastocysts, we generated rat-sized pancreata composed of mouse-PSC-derived cells. Islets subsequently prepared from these mouse-rat chimaeric pancreata were transplanted into mice with streptozotocin-induced diabetes. The transplanted islets successfully normalized and maintained host blood glucose levels for over 370 days in the absence of immunosuppression (excluding the first 5 days after transplant). These data provide proof-of-principle evidence for the therapeutic potential of PSC-derived islets generated by blastocyst complementation in a xenogeneic host.
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Kato-Itoh
authors.affiliation: Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Goto
authors.affiliation: Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Hara
authors.affiliation: Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sanbo
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Yanagida
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Umino
authors.affiliation: Department of Pathology, Research Hospital, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ota
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Sanae
authors.initials: S
authors.lastname: Hamanaka
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Masaki
authors.affiliation: Centre of Stem Cells and Regenerative Medicine and Institute of Liver Studies, King's College London, UK.|Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Sheikh Tamir
authors.initials: ST
authors.lastname: Rashid
authors.affiliation: Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Hirabayashi
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.|Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002678:Chimera; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005260:Female; D064593:Heterografts / Q000276:immunology / Q000502:physiology*; D018398:Homeodomain Proteins; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D008297:Male; D051379:Mice; D038081:Organogenesis; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation; D051381:Rats; D013997:Time Factors; D015534:Trans-Activators / Q000172:deficiency
chemical_list: D001786:Blood Glucose; D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein