Generation of Rat Pancreas in Mouse by Interspecific Blastocyst Injection of Pluripotent Stem Cells

The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative medicine. Mouse wild-type PSCs injected into Pdx1−/− (pancreatogenesis-disabled) mouse blastocysts developmentally compensated vacancy o...

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Published in	Cell Vol. 142; no. 5; pp. 787 - 799
Main Authors	Kobayashi, Toshihiro, Yamaguchi, Tomoyuki, Hamanaka, Sanae, Kato-Itoh, Megumi, Yamazaki, Yuji, Ibata, Makoto, Sato, Hideyuki, Lee, Youn-Su, Usui, Jo-ichi, Knisely, A.S., Hirabayashi, Masumi, Nakauchi, Hiromitsu
Format	Journal Article
Language	English
Published	United States Elsevier Inc 03.09.2010
Subjects	Animals Blastocyst Body size Chimera - embryology DEVBIO Diabetes Mellitus - chemically induced Diabetes Mellitus - therapy Embryonic Development Gene Knock-In Techniques Homeodomain Proteins - genetics Mice Mice, Inbred Strains Organogenesis Pancreas - cytology Pancreas - embryology Pluripotent Stem Cells Rats Rats, Wistar STEMCELL Trans-Activators - genetics STEMCELL DEVBIO
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Abstract	The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative medicine. Mouse wild-type PSCs injected into Pdx1−/− (pancreatogenesis-disabled) mouse blastocysts 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 injected mouse or rat PSCs 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 complementation and for generation in vivo of organs derived from donor PSCs using a xenogenic environment. [Display omitted] ► Pdx1−/− mice provide developmental niche for blastocyst complementation approach ► Mouse pluripotent stem cell (PSC)-derived pancreas is generated in Pdx1−/− mice ► Generation of interspecific chimeras between mouse and rat using PSCs of each ► Generation of rat pancreas in mouse via interspecific blastocyst complementation
AbstractList	The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative medicine. Mouse wild-type PSCs injected into Pdx1 super(-/-) (pancreatogenesis-disabled) mouse blastocysts 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 injected mouse or rat PSCs 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 super(-/-) mouse blastocysts, generating normally functioning rat pancreas in Pdx1 super(-/-) mice. These data constitute proof of principle for interspecific blastocyst complementation and for generation in vivo of organs derived from donor PSCs using a xenogenic environment. The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative medicine. Mouse wild-type PSCs injected into Pdx1(-/-) (pancreatogenesis-disabled) mouse blastocysts 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 injected mouse or rat PSCs 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 complementation and for generation in vivo of organs derived from donor PSCs using a xenogenic environment. The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative medicine. Mouse wild-type PSCs injected into Pdx1−/− (pancreatogenesis-disabled) mouse blastocysts 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 injected mouse or rat PSCs 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 complementation and for generation in vivo of organs derived from donor PSCs using a xenogenic environment. [Display omitted] ► Pdx1−/− mice provide developmental niche for blastocyst complementation approach ► Mouse pluripotent stem cell (PSC)-derived pancreas is generated in Pdx1−/− mice ► Generation of interspecific chimeras between mouse and rat using PSCs of each ► Generation of rat pancreas in mouse via interspecific blastocyst complementation
Author	Hamanaka, Sanae Kato-Itoh, Megumi Lee, Youn-Su Hirabayashi, Masumi Nakauchi, Hiromitsu Usui, Jo-ichi Kobayashi, Toshihiro Yamaguchi, Tomoyuki Yamazaki, Yuji Ibata, Makoto Sato, Hideyuki Knisely, A.S.
Author_xml	– sequence: 1 givenname: Toshihiro surname: Kobayashi fullname: Kobayashi, Toshihiro organization: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 2 givenname: Tomoyuki surname: Yamaguchi fullname: Yamaguchi, Tomoyuki organization: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 3 givenname: Sanae surname: Hamanaka fullname: Hamanaka, Sanae organization: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 4 givenname: Megumi surname: Kato-Itoh fullname: Kato-Itoh, Megumi organization: Japan Science Technology Agency, ERATO, Nakauchi Stem Cell and Organ Regeneration Project, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 5 givenname: Yuji surname: Yamazaki fullname: Yamazaki, Yuji organization: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 6 givenname: Makoto surname: Ibata fullname: Ibata, Makoto organization: Japan Science Technology Agency, ERATO, Nakauchi Stem Cell and Organ Regeneration Project, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 7 givenname: Hideyuki surname: Sato fullname: Sato, Hideyuki organization: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 8 givenname: Youn-Su surname: Lee fullname: Lee, Youn-Su organization: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 9 givenname: Jo-ichi surname: Usui fullname: Usui, Jo-ichi organization: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan – sequence: 10 givenname: A.S. surname: Knisely fullname: Knisely, A.S. organization: Institute of Liver Studies, King's College Hospital, London SE5 9RS, UK – sequence: 11 givenname: Masumi surname: Hirabayashi fullname: Hirabayashi, Masumi organization: Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan – sequence: 12 givenname: Hiromitsu surname: Nakauchi fullname: Nakauchi, Hiromitsu email: nakauchi@ims.u-tokyo.ac.jp organization: Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/20813264$$D View this record in MEDLINE/PubMed
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Snippet	The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative...
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SubjectTerms	Animals Blastocyst Body size Chimera - embryology DEVBIO Diabetes Mellitus - chemically induced Diabetes Mellitus - therapy Embryonic Development Gene Knock-In Techniques Homeodomain Proteins - genetics Mice Mice, Inbred Strains Organogenesis Pancreas - cytology Pancreas - embryology Pluripotent Stem Cells Rats Rats, Wistar STEMCELL Trans-Activators - genetics
Title	Generation of Rat Pancreas in Mouse by Interspecific Blastocyst Injection of Pluripotent Stem Cells
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