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Interspecies organogenesis generates autologous functional islets

Author

Listed:
  • Tomoyuki Yamaguchi

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Hideyuki Sato

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Megumi Kato-Itoh

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Teppei Goto

    (Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences)

  • Hiromasa Hara

    (Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences)

  • Makoto Sanbo

    (Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences)

  • Naoaki Mizuno

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Toshihiro Kobayashi

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Ayaka Yanagida

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Ayumi Umino

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Yasunori Ota

    (Research Hospital, Institute of Medical Science, University of Tokyo)

  • Sanae Hamanaka

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Hideki Masaki

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo)

  • Sheikh Tamir Rashid

    (Centre of Stem Cells and Regenerative Medicine and Institute of Liver Studies, King’s College
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Masumi Hirabayashi

    (Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences)

  • Hiromitsu Nakauchi

    (Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo
    Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

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.

Suggested Citation

  • Tomoyuki Yamaguchi & Hideyuki Sato & Megumi Kato-Itoh & Teppei Goto & Hiromasa Hara & Makoto Sanbo & Naoaki Mizuno & Toshihiro Kobayashi & Ayaka Yanagida & Ayumi Umino & Yasunori Ota & Sanae Hamanaka , 2017. "Interspecies organogenesis generates autologous functional islets," Nature, Nature, vol. 542(7640), pages 191-196, February.
    • Handle: RePEc:nat:nature:v:542:y:2017:i:7640:d:10.1038_nature21070
    DOI: 10.1038/nature21070
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    Cited by:

    1. Hisato Nagano & Naoaki Mizuno & Hideyuki Sato & Eiji Mizutani & Ayaka Yanagida & Mayuko Kano & Mariko Kasai & Hiromi Yamamoto & Motoo Watanabe & Fabian Suchy & Hideki Masaki & Hiromitsu Nakauchi, 2024. "Skin graft with dermis and appendages generated in vivo by cell competition," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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