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Title:
DIFFERENTIATION INDUCTION FROM HUMAN PLURIPOTENT STEM CELLS INTO HYPOTHALAMIC NEURONS
Document Type and Number:
WIPO Patent Application WO/2017/126551
Kind Code:
A1
Abstract:
Provided is a method for efficiently inducing differentiation from human pluripotent stem cells into hypothalamic neurons. Also provided is a method for constructing a cellular structure that integrates pituitary tissue and hypothalamic tissue from human pluripotent stem cells. A cellular structure including hypothalamic tissue is obtained by a method including a step for suspension culturing human pluripotent stem cell spheroids in a medium including a low concentration of an osteogenic factor signaling pathway activator and a low concentration of a substance capable of acting on the Shh signaling pathway, and a step for also suspension culturing the cell spheroids obtained in that step in a medium including a low concentration of a substance capable of acting on the Shh signaling pathway. A cellular structure including hypothalamic tissue and pituitary tissue is also obtained by a method including a step for suspension culturing human pluripotent stem cell spheroids in a medium including an osteogenic factor signaling pathway activator and a substance capable of acting on the Shh signaling pathway, a step for also suspension culturing the cell spheroids formed in that step in a medium including an osteogenic factor signaling pathway activator and a substance capable of acting on the Shh signaling pathway, and a step for suspension culturing the cell spheroids obtained in that step in a medium suitable for simultaneous pituitary and hypothalamic induction .

Inventors:
SUGA HIDETAKA (JP)
OGAWA KOICHIRO (JP)
KASAI TAKATOSHI (JP)
ARIMA HIROSHI (JP)
Application Number:
PCT/JP2017/001544
Publication Date:
July 27, 2017
Filing Date:
January 18, 2017
Export Citation:
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Assignee:
NAT UNIV CORP NAGOYA UNIV (JP)
International Classes:
C12N5/071; C12N1/00; C12N5/02; C12N5/0793
Domestic Patent References:
WO2013065763A12013-05-10
WO2015076388A12015-05-28
WO2014153230A12014-09-25
WO2016013669A12016-01-28
Other References:
OZONE CHIKAFUMI ET AL.: "Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells", NAT. COMMUN., vol. 7, 14 January 2016 (2016-01-14), pages 1 - 10, XP055535023
MERKLE FLORIAN T. ET AL.: "Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells", DEVELOPMENT, vol. 142, 2015, pages 633 - 643, XP055537263
OTSUKA FUMIO: "Multiple Endocrine Regulation by Bone Morphogenetic Protein System", ENDOCRINE JOURNAL, vol. 57, no. 1, 2010, pages 3 - 14, XP055400064
WATAYA TAKAFUMI ET AL.: "Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation", PROC. NATL. ACAD. SCI. USA, vol. 105, no. 33, 2008, pages 11796 - 11801, XP008141896
HIDETAKA SUGA ET AL.: "Self-Formation of Adenohypophysis from Mouse Embryonic Stem Cells", GENDAI IGAKU - CURRENT MEDICINE, vol. 61, no. 2, 1 January 2013 (2013-01-01), pages 191 - 199, XP008185567
WANG YIWEI ET AL.: "Direct and indirect requirements of Shh/Gli signaling in early pituitary development", DEV. BIOL., vol. 348, no. 2, 2010, pages 199 - 209, XP055389459
OCHIAI HIROSHI ET AL.: "BMP4 and FGF strongly induce differentiation of mouse ES cells into oral ectoderm", STEM CELL RESEARCH, vol. 15, 2015, pages 290 - 298, XP029291313
YOSHIKI SASAI: "Shinkeikei Soshiki no Pattern Keisei ni Miru Jiko Soshikika: Sohatsu Seibutsugaku eno Chosen", BRAIN SCIENCE REVIEW, vol. 2014, 2014, pages 99 - 112, XP008185658
See also references of EP 3406709A4
Attorney, Agent or Firm:
HAGINO Mikiharu (JP)
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