Interspecies organogenesis generates autologous functional islets

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, Hideki Masaki, Sheikh Tamir Rashid, Masumi Hirabayashi and Hiromitsu Nakauchi ()
Additional contact information
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
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

Nature, 2017, vol. 542, issue 7640, 191-196

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature21070

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