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eural stem/precursor derived from hiPS cells improved spatial memory learning of dementia model mice

Research Project

Project/Area Number 25505006
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Regenerative medicine
Research InstitutionSt. Marianna University School of Medicine

Principal Investigator

Fujiwara Naruyoshi  聖マリアンナ医科大学, 医学部, 助教 (50365425)

Co-Investigator(Kenkyū-buntansha) Takai Kenji  聖マリアンナ医科大学, 医学部, 教授 (60121167)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords認知症 / 再生医療 / 神経分化誘導 / 神経細胞移植 / ヒトiPS細胞 / 神経分化
Outline of Final Research Achievements

Dementia is a memory loss disorder, which is caused by a variety of brain diseases.There is no fundamental treatment yet. Cell replacement is one of the radical treatments on regenerative medicine and hiPS cells are very useful source for inducing functional cells required for regeneration. We first developed neural stem/progenitor cells from hiPS cells. Then, I transplanted the neuronal precursors into the PDAPP mice brain. Morris water maze test was conducted 14 days before and 45 days after the transplantation to assess the spatial memory and learning of PDAPP mice. After the transplantation, mean platform escape latency of the transplanted PDAPP mice was shorter compared with that of vehicle injected PDAPP mice.The grafted cells differentiated into both cholinergic neurons and GABAergic neurons in the cortex and hippocampus. The restoration of both cholinergic neurons and GABAergic beurons may be importantly associated with the improvement of cognitive dysfunction.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (19 results)

All 2016 2015 2014 2013

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Acknowledgement Compliant: 1 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Cellular and molecular mechanisms of the restoration of human APP transgenic mouse cognitive dysfunction after transplant of human iPS cell-derived neural cells.2015

    • Author(s)
      4.Fujiwara N, Shimizu J, Takai K, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Suzuki N.
    • Journal Title

      Exp Neurol.

      Volume: 2 Pages: 423-431

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sonic Hedgehog Supplementation Rapidly induces Myogenesis in Human Induced Pluripotent Stem Cells.2015

    • Author(s)
      Shiratsuchi T, Misawa H, Fujiwara N, et al.
    • Journal Title

      St. Marianna Medical J

      Volume: 6 Pages: 123-131

    • NAID

      130005114674

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Retinal Progenitor Cell Sheets which Differentiate into Rhodopsin Positive Photoreceptors from Mouse iPS Cell Derived Retinal Progenitor Cell Clones.2015

    • Author(s)
      1.Suzuki N, Shimizu J, Hirotsu C, Takada E, Arimitsu N, Ueda Y, Fujiwara N, SuzukiT, Takai K.
    • Journal Title

      International Journal of Ophthalmology and Clinical Research

      Volume: 2 Pages: 1-5

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induction of neural cells with spinal motoneuron phenotype from human iPS cells and the transplantation to totally transected spinal cords in mice.2015

    • Author(s)
      3.Iinuma M, Umehara T, Arimitsu N, Shimizu J, Misawa H, Takai K, Fujiwara N, Fujii A, UedaY, Wakisaka S, Suzuki T, Hirotsu C, Beppu M, Suzuki N.
    • Journal Title

      Inflammation and Regeneration

      Volume: 35 Pages: 154-163

    • NAID

      130005078573

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Retinal Progenitor Cell Sheets which Differentiate into Rhodopsin Positive Photoreceptors from Mouse iPS Cell Derived Retinal Progenitor Cell Clones2015

    • Author(s)
      Noboru Suzuki, Jun Shimizu, Chieko Hirotsu, Erika Takada, Nagisa Arimitsu, Yuji Ueda, Naruyoshi Fujiwara, Tomoko Suzuki and Kenji Takai
    • Journal Title

      International Journal of Ophthalmology and Clinical Research

      Volume: 2 Pages: 1-6

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pax7 Gene Induction Rapidly Regulates Myocyte Homeostasis in Human Induced Pluripotent Stem (iPS) Cells.2014

    • Author(s)
      Hiroko Misawa, Asako Saito, Jun Shimizu, Masahiro IInuma, Takaki Shiratssuchi, Naruyoshi Fujiwara, Kenji Takai, Nagisa Arimitsu, Yuji Ueda, Dueshige Wakisaka, Tomoko Suzuki, Moroe Beppu, and Noboru Suzuki.
    • Journal Title

      St. Marianna Medical Journal

      Volume: 5 Pages: 59-67

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Restoration of spatial memory dysfunction of human APP transgenic mice by transplantation of neuronal precursors derived from human iPS cells.2013

    • Author(s)
      Fujiwara N, Shimizu J, Takai K, Arimitsu N, Saito A, Kono T, Umehara T, Ueda Y, Wakisaka S, Suzuki T, Suzuki N.
    • Journal Title

      Neurosci Lett.

      Volume: 13 Pages: 947-6

    • DOI

      10.1016/j.neulet.2013.10.043

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] IGFII/Akt Signaling Regulates Myocyte Homeostasis in Human Induced Pluripotent Stem (iPS) Cells.2013

    • Author(s)
      Asako Saito, Jun Shimizu, Naruyoshi Fujiwara, Kenji Takai, Nagisa Arimitsu, Tasuku Umehara, Takao Kono, Hiroko Misawa, Yuji Ueda, Sueshige Wakisaka, Tomoko Suzuki, Moroe Beppu, Noboru Suzuki.
    • Journal Title

      St. Marianna Medical J

      Volume: 4 Pages: 41-48

    • NAID

      40019942512

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human iPS Cell Derived Neurons with Cortical Motor Neuron Phenotype are Relevant for Functional Recovery of Hemiplegic Mice with Injured Motor Cortex.2013

    • Author(s)
      3. Takao Kono, Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Naruyoshi Fujiwara, Tasuku Umehara, Asako Saito, Yuji Ueda, Sueshige Wakisaka, Tomoko Suzuki, Takuo Hashimoto, Yuichiro Tanaka, Noboru Suzuki.
    • Journal Title

      St. Marianna Medical J

      Volume: 4 Pages: 31-40

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transplantation of Motor Neurons Derived from Human iPS Cells into Total Transection Model of Spinal Cord Injury in Mice.2013

    • Author(s)
      4. Tasuku Umehara, Nagisa Arimitsu, Masahiro Iinuma, Jun Shimizu, Kenji Takai, Naruyoshi Fujiwara, Asako Saito, Takao Kono, Yuji Ueda, Sueshige Wakisaka, Tomoko Suzuki, Moroe Beppu, Noboru Suzuki.
    • Journal Title

      St. Marianna Medical J

      Volume: 4 Pages: 21-30

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Restoration of human APP transgenic mouse cognitive dysfunction after transplant of human iPS cell-derived neural stem/precursor cells.2016

    • Author(s)
      Naruyoshi Fujiwara, Kenji Takai, Erika Takada, Chieko Hirotsu, Nagisa Arimitsu, Jun Shimizu and Noboru Suzuki
    • Organizer
      INTERNATIONAL SOCIETY FOR STEM CELL RESERCH 14th ANNUAL MEETING
    • Place of Presentation
      SAN FRANCISCO CALIFORNIA (USA)
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human iPS derived neural stem/precursor improved spatial memory learning of dementia model mice.2015

    • Author(s)
      Fujiwara, Naruyoshi, Takai, Kenji, Suzuki, Chika, Hirotsu, Chieko, Takada, Erika, Arimitsu, Nagisa, Shimizu, Jun, Suzuki, Noboru
    • Organizer
      ERNATIONAL SOCIETY FOR STEM CELL RESERCH 13th ANNUAL MEETING
    • Place of Presentation
      STOCKHOLM SWEDEN
    • Year and Date
      2015-06-24 – 2015-06-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Human iPS derived neural stem/precursor improved spatial memory learning of dementia model mice.2015

    • Author(s)
      Naruyoshi Fujiwara, Chika Suzuki, Kenji Takai, Erika Takada, Chieko Hirotsu, Nagisa Arimitsu, Jun Shimizu and Noboru Suzuki
    • Organizer
      INTERNATIONAL SOCIETY FOR STEM CELL RESERCH 13th ANNUAL MEETING
    • Place of Presentation
      STOCKHOLM (SWEDEN)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトiPS細胞から誘導した神経細胞移植による認知機能の改善とそのメカニズムについての検討2015

    • Author(s)
      藤原成芳、高井憲司、鈴木千佳、広津千恵子、高田えりか、有光なぎさ、白土崇輝、清水潤、鈴木登
    • Organizer
      第111回日本精神神経学会
    • Place of Presentation
      大阪国際会議場 (大阪)
    • Year and Date
      2015-06-04 – 2015-06-06
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒトiPS由来神経細胞移植による空間記憶能の改善と改善メカニズムについての検討2015

    • Author(s)
      藤原成芳、高井憲司、鈴木千佳、広津千恵子、高田えりか、有光なぎさ、白土崇輝、清水潤、鈴木登
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜 (横浜)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Research-status Report
  • [Presentation] Restoration of spatial memory dysfunction of human APP transgenic mice by transplantation of neuronal precursors derived from human iPS cells2014

    • Author(s)
      Naruyoshi Fujiwara, Kenji Takai, Erika Takada, Chieko Hirotsu, Nagisa Arimitsu, Jun Shimizu, Noboru Suzuki.
    • Organizer
      INTERNATIONAL SOCIETY FOR STEM CELL RESERCH 12th ANNUAL MEETING
    • Place of Presentation
      VANCOUVER CANADA
    • Year and Date
      2014-06-18 – 2014-06-21
    • Related Report
      2014 Research-status Report
  • [Presentation] DIFFERENTIATION OF CHOLINERGIC NEURONS FROM HIPS CELLS AND RESTORATION OF COGNITIVE FUNCTION BY THEIR TRANSPLANTATION IN MICE WITH DEMENTIA2013

    • Author(s)
      Naruyoshi Fujiwara, Kenji Takai, Erika Takada, Chieko Hirotsu, Nagisa Arimitsu, Asako Saito, Jun Shimizu, Noboru Suzuki.
    • Organizer
      INTERNATIONAL SOCIETY FOR STEM CELL RESERCH 11TH ANNUAL MEETING
    • Place of Presentation
      BOSTON, MA USA
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトiPS細胞から誘導した神経細胞移植によるヒトAPPトランスジェニックマウスにおける空間記憶能の改善の検討2013

    • Author(s)
      藤原成芳、高井憲司、高田えりか、廣津千恵子、斉藤亜沙子、有光なぎさ、梅原亮、神野崇、清水潤、鈴木登
    • Organizer
      第34回 日本炎症・再生医学会
    • Place of Presentation
      京都国際会館
    • Related Report
      2013 Research-status Report
  • [Presentation] ヒトiPS細胞から誘導した神経細胞移植による認知機能改善効果の検討2013

    • Author(s)
      藤原成芳、高井憲司、高田えりか、廣津千恵子、斉藤亜沙子、有光なぎさ、神野崇生、清水潤、鈴木登
    • Organizer
      第109回 日本精神神経学会学術総会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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