Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells

Chikafumi Ozone, Hidetaka Suga (), Mototsugu Eiraku, Taisuke Kadoshima, Shigenobu Yonemura, Nozomu Takata, Yutaka Oiso, Takashi Tsuji and Yoshiki Sasai
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Chikafumi Ozone: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Hidetaka Suga: Graduate School of Medicine, Nagoya University
Mototsugu Eiraku: Laboratory for In Vitro Histogenesis, RIKEN Center for Developmental Biology
Taisuke Kadoshima: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Shigenobu Yonemura: Electron Microscope Laboratory, RIKEN Center for Developmental Biology
Nozomu Takata: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology
Yutaka Oiso: Graduate School of Medicine, Nagoya University
Takashi Tsuji: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology
Yoshiki Sasai: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract Anterior pituitary is critical for endocrine systems. Its hormonal responses to positive and negative regulators are indispensable for homeostasis. For this reason, generating human anterior pituitary tissue that retains regulatory hormonal control in vitro is an important step for the development of cell transplantation therapy for pituitary diseases. Here we achieve this by recapitulating mouse pituitary development using human embryonic stem cells. We find that anterior pituitary self-forms in vitro following the co-induction of hypothalamic and oral ectoderm. The juxtaposition of these tissues facilitated the formation of pituitary placode, which subsequently differentiated into pituitary hormone-producing cells. They responded normally to both releasing and feedback signals. In addition, after transplantation into hypopituitary mice, the in vitro-generated corticotrophs rescued physical activity levels and survival of the hosts. Thus, we report a useful methodology for the production of regulator-responsive human pituitary tissue that may benefit future studies in regenerative medicine.

Date: 2016
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DOI: 10.1038/ncomms10351

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