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Development of a novel therapy for perinatal brain injury with dedifferentiated fat cells

Research Project

Project/Area Number 26461630
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionNagoya University

Principal Investigator

Sato Yoshiaki  名古屋大学, 医学部附属病院, 講師 (30435862)

Co-Investigator(Renkei-kenkyūsha) MATSUMOTO TARO  日本大学, 医学部, 教授 (50366580)
TSUHI MASAHIRO  独立行政法人国立循環器病研究センター, 再生医療部, 室長 (80579467)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords低酸素性虚血性脳症 / 幹細胞 / 新生児低酸素性虚血性脳症 / 脱分化脂肪細胞 / 周産期低酸素性虚血性脳症
Outline of Final Research Achievements

In the present study, we aimed to determine whether the outcome of HIE can be improved by DFAT cell treatment. 24 h after HI insult, DFAT cells were injected at 10^5 cells/pup into the right external jugular vein. The number of cells that stained positive for active caspase-3, ED-1, and 4-HNE decreased in the DFAT-treated group. The HI insult led to a motor deficit according to the rotarod treadmill and cylinder test, where it significantly affected the vehicle group, whereas no difference was confirmed between the DFAT and sham groups. According to in vitro experiments, the cell death rates in the DFAT-CM-treated cells were significantly lower than those in the controls. In the DFAT-CM, several neurotrophic factors, IGF-1、NGF、NT3 were detected, and these factors were increased in the ipsilateral brain after injection of DFAT. Our results indicate that intravenous injection with DFAT cells is effective for ameliorating HI brain injury, possibly via paracrine effects.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (27 results)

All 2017 2016 2015 2014

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 2 results) Presentation (17 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results)

  • [Journal Article] Dedifferentiated fat cells, as a novel source for cell therapy to target neonatal hypoxic ischemic encephalopathy.2017

    • Author(s)
      Mikrogeorgiou A, Kondo T, Hattori T, Sugiyama Y, Nakanishi K, Tsuji M, Kazama T, Kano K, Matsumoto T, Hayakawa M, Sato Y
    • Journal Title

      Developmental Neuroscience

      Volume: 印刷中 Issue: 1-4 Pages: 273-286

    • DOI

      10.1159/000455836

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multicenter observational study comparing sedation/analgesia protocols for laser photocoagulation treatment of retinopathy of prematurity.2015

    • Author(s)
      Sato Y, Oshiro M, Takemoto K, Hosono H, Saito A, Kondo T, Aizu K, Matsusawa M, Futamura Y, Asami T, Terasaki H, Hayakawa M.
    • Journal Title

      J Perinatol.

      Volume: 35 Issue: 11 Pages: 965-9

    • DOI

      10.1038/jp.2015.112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ntraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia2015

    • Author(s)
      Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M
    • Journal Title

      Brain Dev

      Volume: 37 Issue: 4 Pages: 376-386

    • DOI

      10.1016/j.braindev.2014.06.010

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Maternal molecular hydrogen administration on lipopolysaccharide-induced mouse fetal brain injury2015

    • Author(s)
      Nakano T, Kotani T, Mano Y, Tsuda H, Imai K, Ushida T, Li H, Miki R, Sumigama S, Sato Y, Iwase A, Hirakawa A, Asai M, Toyokuni S, Kikkawa F.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 57 Issue: 3 Pages: 178-182

    • DOI

      10.3164/jcbn.15-90

    • NAID

      130005106454

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury.2015

    • Author(s)
      Hattori Y, Kotani T, Tsuda H, Mano Y, Tu L, Li H, Hirako S, Ushida T, Imai K, Nakano T, Sato Y, Miki R, Sumigama S, Iwase A, Toyokuni S, Kikkawa F.
    • Journal Title

      Free radical research.

      Volume: 49 Issue: 8 Pages: 1026-37

    • DOI

      10.3109/10715762.2015.1038257

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Administration of umbilical cord blood cells transiently decreased hypoxic-ischemic brain injury in neonatal rats2015

    • Author(s)
      Hattori, T. Sato, Y. Kondo, T. Ichinohashi, Y. Sugiyama, Y. Yamamoto, M. Kotani, T. Hirata, H. Hirakawa, A. Suzuki, S. Tsuji, M. Ikeda, T. Nakanishi, K. Kojima, S. Blomgren, K. Hayakawa, M.
    • Journal Title

      Dev Neurosci

      Volume: 37 Issue: 2 Pages: 95-104

    • DOI

      10.1159/000368396

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Buckling surgery and supplemental intravitreal bevacizumab or photocoagulation on stage 4 retinopathy of prematurity eyes. Japanese journal of ophthalmology.2015

    • Author(s)
      Futamura Y, Asami T, Nonobe N, Kachi S, Ito Y, Sato Y, Hayakawa M, Terasaki H.
    • Journal Title

      Japanese journal of ophthalmology.

      Volume: 59 Issue: 6 Pages: 378-88

    • DOI

      10.1007/s10384-015-0401-5

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of intravenous administration of umbilical cord blood CD34+ cells in a mouse model of neonatal stroke.2014

    • Author(s)
      Tsuji M, Taguchi A, Ohshima M, Kasahara Y, Sato Y, Tsuda H, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T.
    • Journal Title

      Neuroscience

      Volume: 263 Pages: 148-158

    • DOI

      10.1016/j.neuroscience.2014.01.018

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of placenta previa on neonatal respiratory disorders and amniotic lamellar body counts at 36-38weeks of gestation2014

    • Author(s)
      Tsuda H, Kotani T, Sumigama S, Mano Y, Hua L, Hayakawa H, Hayakawa M, et al.
    • Journal Title

      Early Hum Dev

      Volume: 90(1) Issue: 1 Pages: 51-4

    • DOI

      10.1016/j.earlhumdev.2013.10.005

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Paradoxical downward seizure pattern on amplitude-integrated electroencephalogram.2014

    • Author(s)
      Ito M, Kidokoro H, Sugiyama Y, Sato Y, Natsume J, Watanabe K, Hayakawa M.
    • Journal Title

      J Perinatol.

      Volume: 34 Issue: 8 Pages: 642-4

    • DOI

      10.1038/jp.2013.84

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Intravenous injection with dedifferentiated fat cells ameliorated neonatal hypoxic ischemic brain injury, possibly via paracrine effects2017

    • Author(s)
      Yoshiaki Sato, Alkisti Mikrogeorgiou, Taiki Kondo, Tetsuo Hattori, Yuichiro Sugiyama, Keiko Nakanishi, Masahiro Tsuji, Tomohiko Kazama, Koichiro Kano, Taro Matsumoto, Masahiro Hayakawa
    • Organizer
      International Society for Stem Cell Research Annual meeting
    • Place of Presentation
      ボストン(米国)
    • Year and Date
      2017-06-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dedifferentiated fat cells, as a novel source for cell therapy to target neonatal hypoxic ischemic encephalopathy2017

    • Author(s)
      Alkisti Mikrogeorgiou, Yoshiaki Sato, Taiki Kondo, Tetsuo Hattori, Yuichiro Sugiyama, Keiko Nakanishi, Masahiro Tsuji, Tomohiko Kazama, Koichiro Kano, Taro Matsumoto, Masahiro Hayakawa
    • Organizer
      Pediatric Academic Societies Meeting
    • Place of Presentation
      サンフランシスコ(米国)
    • Year and Date
      2017-05-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 周産期低酸素性虚血性脳症に対する脱分化脂肪細胞を用いた新規治療法の開発2017

    • Author(s)
      佐藤義朗
    • Organizer
      第16回日本再医療学会総会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Administration of mature adipocyte-derived cells, dedifferentiated fat cells (DFAT), decreases hypoxic-ischemic brain injury in neonatal rats.2016

    • Author(s)
      佐藤義朗、Alkisti Mikrogeorgiou、近藤大貴、杉山裕一朗、鈴木俊彦、北瀬悠磨、見松はるか、風間智彦、松本太郎、加野浩一郎、辻 雅弘、中西圭子、早川昌弘
    • Organizer
      第36回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] Dedifferentiated fat cells as a treatment for perinatal hypoxic ischemic brain injury2016

    • Author(s)
      Alkisti Mikrogeorgiou, Yoshiaki Sato, Taiki Kondo, Yuichiro Sugiyama, Keiko Nakanishi, Masahiro Tsuji, Tomohiko Kazama, Taro Matsumoto, Koichiro Kano, Masahiro Hayakawa
    • Organizer
      10th Hershey Conference on Developmental Brain Injury
    • Place of Presentation
      パリ(フランス)
    • Year and Date
      2016-06-08
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dedifferentiated fat cells, a novel source for cell therapy to target neonatal hypoxia-ischemia2016

    • Author(s)
      Mikrogeorgiou Alkisti 、佐藤義朗、杉山裕一郎  鈴木俊彦 北瀬悠磨 近藤大貴 中西圭子、 辻雅弘、風間智彦 、松本太郎、加野浩一郎、早川昌弘
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 新生児低酸素性虚血性脳症に対する自己臍帯血幹細胞治療の臨床試験2015

    • Author(s)
      佐藤義朗, 辻雅弘, 鍋谷まこと, 市場博幸, 岡 明, 田村正徳, 濱崎考史, 北島博之, 船戸正久, 田口明彦, 楠田聡, 森臨太郎, 早川昌弘, 渡部晋一, 新宅治夫
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Research-status Report
  • [Presentation] 「HIEのこれからの治療」幹細胞療法の基礎研究2014

    • Author(s)
      佐藤義朗
    • Organizer
      第59回日本未熟児新生児学会
    • Place of Presentation
      愛媛県民文化会館(愛媛県松山市)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 新生児低酸素性虚血性脳症モデルラットにおける骨髄単核球静脈内投与の治療効果2014

    • Author(s)
      近藤大貴, 佐藤義朗, 杉山裕一朗, 鈴木俊彦, 北瀬悠磨, 片岡英里奈, 伊藤美春, 齊藤明子, 孫田みゆき, 村松友佳子, 辻雅弘, 中西圭子, 早川昌弘
    • Organizer
      第59回日本未熟児新生児学会
    • Place of Presentation
      愛媛県民文化会館(愛媛県松山市)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 早産児と正期産児におけるProton MR spectroscopyの比較検討2014

    • Author(s)
      兵藤玲奈, 佐藤義朗, 伊藤美春, 杉山裕一朗, 鈴木俊彦, 北瀬悠磨, 齊藤明子, 近藤大貴, 孫田みゆき, 村松友佳子, 城所博之, 早川昌弘
    • Organizer
      第59回日本未熟児新生児学会
    • Place of Presentation
      愛媛県民文化会館(愛媛県松山市)
    • Year and Date
      2014-11-10 – 2014-11-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 低血糖を呈する遅発性進行性周産期脳障害2014

    • Author(s)
      佐藤義朗
    • Organizer
      第29回日本母乳哺育学会・学術集会
    • Place of Presentation
      横浜市教育会館(神奈川県横浜市)
    • Year and Date
      2014-10-11 – 2014-10-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Methylxanthines (theophylline and caffeine) suppress neurogenesis in the immature brain2014

    • Author(s)
      佐藤義朗, 中西圭子, 伊藤美春, 早川昌弘
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] ステロイドホルモン投与の未熟脳への影響 ~動物モデルから~2014

    • Author(s)
      佐藤義朗, 中村祐子, 早川昌弘
    • Organizer
      第50回日本周産期・新生児医学会学術集会
    • Place of Presentation
      シェラトン・グランデ・トーキョーベイ・ホテル(千葉県浦安市)
    • Year and Date
      2014-07-13 – 2014-07-15
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] HIEモデルマウスにおける抗IL-6 レセプター抗体の効果2014

    • Author(s)
      齊藤明子, 佐藤義朗, 鈴木俊彦, 杉山裕一朗, 伊藤美春, 孫田みゆき, 近藤大貴, 藤巻英彦, 中村裕子, 早川昌弘
    • Organizer
      第50回日本周産期・新生児医学会学術集会
    • Place of Presentation
      シェラトン・グランデ・トーキョーベイ・ホテル(千葉県浦安市)
    • Year and Date
      2014-07-13 – 2014-07-15
    • Related Report
      2014 Research-status Report
  • [Presentation] 臍帯血細胞を用いた周産期低酸素性虚血性脳症に対する治療2014

    • Author(s)
      佐藤義朗, 服部哲夫, 近藤大貴, Alkisti Mikrogeorgiou、杉山裕一朗、 小谷友美, 辻雅弘, 中西圭子, 早川昌弘
    • Organizer
      第2回臍帯血による再生医療研究会学術集会
    • Place of Presentation
      山王病院(東京都港区)
    • Year and Date
      2014-07-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Administration of umbilical cord blood cells decreases hypoxic-ischemic brain injury in neonatal rats.2014

    • Author(s)
      Sato Y, Hattori T, Kondo T, Ichinohashi Y, Sugiyama Y, Tsuji M, Ikeda T, Nakanishi K, Blomgren K, Hayakawa M
    • Organizer
      9th Hershey Conference on Developmental Brain Injury
    • Place of Presentation
      Saint Michael, USA
    • Year and Date
      2014-06-02 – 2014-06-08
    • Related Report
      2014 Research-status Report
  • [Presentation] 周産期脳障害に対する幹細胞療法2014

    • Author(s)
      佐藤義朗
    • Organizer
      第117回日本小児科学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2014-04-11 – 2014-04-13
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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