The regenerative therapy for central diabetes insipidus

• Project/Area Number: 22390188
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Nagoya University
• Principal Investigator: OISO Yutaka 名古屋大学, 医学系研究科, 教授 (40203707)
• Co-Investigator(Kenkyū-buntansha): NAGASAKI Hiroshi 藤田保健衛生大学, 医学部, 准教授 (30420384) ; SUGA Hidetaka 名古屋大学, 医学部附属病院, 病院助教 (20569818)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 再生医学 / 中枢性尿崩症 / 生理活性 / バゾプレシン / 再生医療 / 細胞移植 / マウスES細胞 / 無血清浮遊培養法 / 視床下部前駆細胞

Research Abstract

It is known mouse embryonic stem cell can be developed into hypothalamic lineage (ES-hypo) invitro. In this study, we have improved the method to have vasopressin neurons more effectively. Central diabetes insipidus manifests polyuria and polydipsia which results from the deficit in the hypothalamic area that produce vasopressin. We have developed a regenerativetherapy using ES-hypo in the model animal, Brattleboro rat. The heterograft of ES-hypo in the brain survived more than six weeks, and recipients reduced urine volume by 40% compared to the negative control group.

Research Products

• [Journal Article] Lesion of area postrema attenuated hyperphagic responses to glucoprivation, but not transcriptional activation of the neuropeptide Y gene in rats. (2012)
  • Author(s): Ozawa Y, Arima H, Banno R, Ito Y, Goto M, Morishita Y, Sugimura Y, Ozaki N, Nagasaki H, Oiso Y
  • Journal Title: Neuroreport Volume: 23(11) Pages: 673-5
  • Peer Reviewed
• [Journal Article] BiP mRNA expression is upregulated by dehydration in vasopressin neurons in the hypothalamus in mice (2012)
  • Author(s): Hagiwara D, Arima H, Morishita Y, Goto M, Banno R, Sugimura Y, Oiso Y
  • Journal Title: Peptides Volume: 33(2) Pages: 346-50
  • Peer Reviewed
• [Journal Article] TNFαincreases hypothalamic PTP1B activity via the NFκB pathway in rat hypothalamic organotypic cultures (2012)
  • Author(s): Ito Y, Banno R, Hagimoto S, Ozawa Y, Arima H, Oiso Y.
  • Journal Title: Regul Pept Volume: 174(1-3) Pages: 58-64
  • Peer Reviewed
• [Journal Article] BiP mRNA expression is upregulated by dehydration in vasopressin neurons in the hypothalamus in mice. (2012)
  • Author(s): Hagiwara D
  • Journal Title: Peptides Volume: 33 Pages: 346-50
  • Peer Reviewed
• [Journal Article] TNFα increases hypothalamic PTP1B activity via the NFκB pathway in rat hypothalamic organotypic cultures. (2012)
  • Author(s): Ito Y
  • Journal Title: Regul Pept. Volume: 174 Pages: 58-64
  • Peer Reviewed
• [Journal Article] BiP mRNA expression is upregulated by dehydration in vasopressin neurons in the hypothalamus in mice (2012)
  • Author(s): Hagiwara D, Oiso Y, et al
  • Journal Title: Peptides Volume: (in press)
  • Peer Reviewed
• [Journal Article] Self-formation of functional adenohypophysis in three-dimensional culture (2011)
  • Author(s): Suga H, Kadoshima T, Minaguchi M, Ohgushi M, Soen M, Nakano T, Takata N, Wataya T, Muguruma K, Miyoshi H, Yonemura S, Oiso Y, Sasai Y
  • Journal Title: Nature Volume: 480(7375) Pages: 57-62
  • Peer Reviewed
• [Journal Article] Poly(A)tail length of neurohypophysial hormones is shortened under endoplasmic reticulum stress. (2011)
  • Author(s): Morishita Y, Arima H, Hiroi M, Hayashi M, Hagiwara D, Asai N, Ozaki N, Sugimura Y, Nagasaki H, Shiota A, Takahashi M, Oiso Y
  • Journal Title: Endocrinology Volume: 152(12) Pages: 4846-55
  • Peer Reviewed
• [Journal Article] Repeated glucoprivation delayed hyperphagic responses while activating neuropeptide Y neurons in rats. (2011)
  • Author(s): Ozawa Y, Arima H, Watanabe M, Shimizu H, Ito Y, Banno R, Sugimura Y, Ozaki N, Nagasaki H, Oiso Y
  • Journal Title: Peptides Volume: 32(4) Pages: 763-9
  • Peer Reviewed
• [Journal Article] Time-dependent changes in proinflammatory and neurotrophic responses of microglia and astrocytes in a rat model of osmotic demyelination syndrome (2011)
  • Author(s): Iwama S, Sugimura Y, Suzuki H, Suzuki H, Murase T, Ozaki N, Nagasaki H, Arima H, Murata Y, Sawada M, Oiso Y.
  • Journal Title: Glia Volume: 59(3) Pages: 452-62
  • Peer Reviewed
• [Journal Article] Self-formation of functional adenohypophysis in three-dimensional culture (2011)
  • Author(s): Suga H, Oiso Y, et al
  • Journal Title: Nature Volume: 480 Issue: 7375 Pages: 57-62
  • DOI: 10.1038/nature10637
  • Peer Reviewed
• [Journal Article] Low-serum culture system improves the adipogenic ability of visceral adipose tissue-derived stromal cells (2011)
  • Author(s): 長崎弘, 他
  • Journal Title: Cell Biology International Volume: 35 Issue: 6 Pages: 559-568
  • DOI: 10.1042/cbi20100406
  • Peer Reviewed
• [Journal Article] Minocycline Prevents Osmotic Demyelination Syndrome by Inhibiting the Activation of Microglia. (2010)
  • Author(s): Suzuki H, Sugimura Y, Iwama S, Suzuki H, Nobuaki O, Nagasaki H, Arima H, Sawada M, Oiso Y
  • Journal Title: J Am Soc Nephrol Volume: 21(12) Pages: 2090-8
  • Peer Reviewed
• [Journal Article] Mechanisms Underlying Progressive Polyuria in Familial Neurohypophysial Diabetes Insipidus (2010)
  • Author(s): Arima H, Oiso Y
  • Journal Title: J Neuroendocrinol Volume: 22(7) Pages: 754-7
  • Peer Reviewed
• [Journal Article] Activation of vasopressin neurons leads to phenotype progression in a mouse model for familial neurohypophysial diabetes insipidus. (2010)
  • Author(s): Hiroi M, Morishita Y, Hayashi M, Ozaki N, Sugimura Y, Nagasaki H, Shiota A, Oiso Y,Arima H.
  • Journal Title: Am J Physiol Regul Integr Comp Physiol Volume: 298(2)
  • Peer Reviewed
• [Journal Article] Minocycline Prevents Osmotic Demyelination Syndrome by Inhibiting the Activation of Microglia. (2010)
  • Author(s): 大磯ユタカ, 他
  • Journal Title: Journal of the American Society of Nephrology Volume: 21 Pages: 2090-2098
  • Peer Reviewed
• [Journal Article] Activation of vasopressin neurons leads to phenotype progression in amouse model for familial neurohypophysial diabetes insipidus. (2010)
  • Author(s): 大磯ユタカ, 他
  • Journal Title: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Volume: 298
  • Peer Reviewed
• [Journal Article] Comparison of the effects of three angiotensin II receptor type 1 blockers on metabolic parameters in hypertensive patients with type 2 diabetes mellitus. (2010)
  • Author(s): 大磯ユタカ, 他
  • Journal Title: European Journal of Internal Medicine Volume: 21 Pages: 236-239
  • Peer Reviewed
• [Journal Article] Protective Effect of Hedgehog Signaling on Cytokine-Induced Cytotoxicity in Pancreatic Beta-Cells. (2010)
  • Author(s): 大磯ユタカ, 他
  • Journal Title: Experimental and Clinical Endocrinology & Diabetes Volume: 118 Pages: 692-698
  • Peer Reviewed
• [Journal Article] Mechanisms Underlying Progressive Polyuria in Familial Neurohypophysial Diabetes Insipidus. (2010)
  • Author(s): 大磯ユタカ, 他
  • Journal Title: Journal of Neuroendocrinology Volume: 22 Pages: 754-757
  • Peer Reviewed
• [Presentation] マウスES細胞由来視床下部誘導系におけるバゾプレシン細胞の解析 (2012)
  • Author(s): 長崎 弘,福岡一貴,小谷 侑、須賀英隆、笹井芳樹、金子葉子、中島 顕, 大磯ユタカ、太田 明
  • Organizer: 第59回中部日本生理学会
  • Place of Presentation: 自然科学研究機構岡崎コンファレンスセンター
  • Year and Date: 2012-11-17
• [Presentation] マウスES細胞由来視床下部細胞系による中枢性尿崩症治療 (2012)
  • Author(s): 福岡一貴、長崎 弘、須賀英隆、清田篤志、椙村益久、有馬寛、笹井芳樹、大磯ユタカ
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-09-18
• [Presentation] 再生医療による中枢性尿崩症治療法の開発 (2012)
  • Author(s): 福岡一貴、大磯ユタカ, 他
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場(発表確定)
  • Year and Date: 2012-04-21
• [Presentation] マウスES細胞由来-視床下部培養系における視床下部ニューロンの発生 (2012)
  • Author(s): 長崎弘、大磯ユタカ, 他
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場(発表確定)
  • Year and Date: 2012-04-21
• [Presentation] マウスES 細胞由来-視床下部培養系における視床下部ニューロンの発生 (2012)
  • Author(s): 長崎 弘大磯ユタカ
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-04-20
• [Presentation] 再生医療による中枢性尿崩症治療法の開発 (2012)
  • Author(s): 福岡一貴,長崎 弘、大磯ユタカ
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2012-04-20
• [Presentation] 再生医療による中枢性尿崩症治療法の開発 (2012)
  • Author(s): 長崎 弘
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Invited
• [Presentation] マウスES 細胞由来―視床下部培養系における視床下部ニューロンの発生 (2012)
  • Author(s): 長崎 弘
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] マウスES細胞由来視床下部細胞系による中枢性尿崩症治療 (2012)
  • Author(s): 長崎 弘
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Presentation] マウスES細胞由来視床下部誘導系におけるバゾプレシン細胞の解析 (2012)
  • Author(s): 長崎 弘
  • Organizer: 第59回中部日本生理学会
  • Place of Presentation: 自然科学研究機構生理学研究所（岡崎）
• [Presentation] 先端巨大症における薬物治療効果の検討 (2011)
  • Author(s): 大磯ユタカ, 他
  • Organizer: 第20回臨床内分泌代謝Update
  • Place of Presentation: 札幌コンベンションセンター(札幌)
• [Presentation] AVP遺伝子SP変異による家族性中枢性尿崩症の母子例 (2011)
  • Author(s): 大磯ユタカ, 他
  • Organizer: 第20回臨床内分泌代謝Update
  • Place of Presentation: 札幌コンベンションセンター(札幌)
• [Presentation] comparative analysis of gene expression profiles of microglia from demyelinative lesions in osmotic demyelination syndrome rat model. (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: 10th International Congress of Neuroimmunology
  • Place of Presentation: Barcelona(Spain)
  • Year and Date: 2010-10-27
• [Presentation] Gene expression profiling of microglia from the demyelinative lesions in osmotic demyelination syndrome (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: Neuro 2010
  • Place of Presentation: 神戸コンベンションセンター(神戸)
  • Year and Date: 2010-09-02
• [Presentation] Mechanisms underlying progressive polyuria in a mouse model for familial neurohypophysial diabetes insipidus. (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: The 7th International Congress of Neuroendocrinology
  • Place of Presentation: Rouen(France)
• [Presentation] Posttranscriptional regulation of vasopressin mRNA in a mouse model for familial neurohypophysial diabetes insipidus. (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: The 7th International Congress of Neuroendocrinology
  • Place of Presentation: Rouen(France)
• [Presentation] Repeated glucoprivation delayed feeding responses in rats. (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: The 7th International Congress of Neuroendocrinology
  • Place of Presentation: Rouen(France)
• [Presentation] TNFαは視床下部においてレプチンシグナルを阻害するPTPIBの活性を増強する (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテルグランヴィア岡山(岡山)
• [Presentation] 糖欠乏状態の反復による摂食反応の遅延には脳幹部におけるカテコラミンニューロンの脱感作が関与する (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテルグランヴィア岡山(岡山)
• [Presentation] TNFαは視床下部においてレプチンシグナルを阻害するPTPIBの活性を増強する (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: 第31回日本肥満学会
  • Place of Presentation: 前橋テルサ(群馬)
• [Presentation] TNFαによる視床下部PTPIBの発現および活性調節 (2010)
  • Author(s): 大磯ユタカ, 他
  • Organizer: 第37回日本神経内分泌学会学術集会
  • Place of Presentation: 京都大学医学部芝蘭会館(京都)