title: Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells.
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.
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.|Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.|Department of Endocrinology and Diabetes, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
authors.forename: Chikafumi
authors.initials: C
authors.lastname: Ozone
authors.affiliation: Department of Endocrinology and Diabetes, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Suga
authors.affiliation: Laboratory for In Vitro Histogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Eiraku
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kadoshima
authors.affiliation: Electron Microscope Laboratory, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.|CREST, Japan Science and Technology Agency, Kobe 650-0047, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.|Laboratory for In Vitro Histogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Takata
authors.affiliation: Department of Endocrinology and Diabetes, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.affiliation: Laboratory for Organ Regeneration, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sasai
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D052680:Corticotrophs / Q000637:transplantation*; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007018:Hypopituitarism / Q000628:therapy*; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000196:embryology* / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone