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

• Project/Area Number: 25505006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Regenerative medicine
• Research Institution: St. 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: ¥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.

Research Products

• [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
  • 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
  • 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
  • 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
  • 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): 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
  • 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
• [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
• [Presentation] Restoration of spatial memory dysfunction of human APP transgenic mice by transplantation of neuronal precursors derived from human iPS cells (2014)
  • 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
• [Presentation] DIFFERENTIATION OF CHOLINERGIC NEURONS FROM HIPS CELLS AND RESTORATION OF COGNITIVE FUNCTION BY THEIR TRANSPLANTATION IN MICE WITH DEMENTIA (2013)
  • 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
• [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
• [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