Safety and effectiveness of neural stem cells directly induced from skin fibroblasts

• Project/Area Number: 23618010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Regenerative medicine
• Research Institution: Keio University
• Principal Investigator: AKAMATSU WADO 慶應義塾大学, 医学部, 講師 (60338184)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経幹細胞 / ダイレクトリプログラミング / リプログラミング / 直接誘導 / iPS細胞

Research Abstract

We succeeded in making human directly induced neural stem cells by using Sendai virus vectors. Although we were able to obtain increased number of neurospheres compared to retroviral vectors, SeV-induced neurospheres did not differentiate into neural cells efficiently.

Research Products

• [Journal Article] Involvement of ER Stress in Dysmyelination of Pelizaeus-Merzbacher Disease with PLP1 Missense Mutations Shown by iPSC-Derived Oligodendrocytes (2014)
  • Author(s): Numasawa-Kuroiwa Y, Okada Y, Shibata S, Kishi N, Akamatsu W, Shoji M, Nakanishi A, Oyama M, Oasaka H, Inoue K, Takahashi K, Yamanaka S, Kosaki K, Takahashi T, Okano H
  • Journal Title: Stem Cell Rep Volume: 2 Issue: 5 Pages: 1-14
  • DOI: 10.1016/j.stemcr.2014.03.007
  • Peer Reviewed / Open Access
• [Journal Article] Reprogramming non-human primate somatic cells into functional neuronal cells by defined factors. (2014)
  • Author(s): Zhou Z, Kohda K, Ibata K, Kohyama J, Akamatsu W, Yuzaki M, Okano HJ, Sasaki E, Okano H
  • Journal Title: Molecular Brain Volume: 3 Issue: 1 Pages: 724-724
  • DOI: 10.1186/1756-6606-7-24
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prenatal deletion of the RNA binding protein HuD disrupts postnatal cortical circuit maturation and behavior (2014)
  • Author(s): DeBoer E, Azevedo R, Vega T, Brodkin J, Akamatsu W, Okano H, Wagner G, Rasin MR
  • Journal Title: J Neurosci Volume: 34(10) Pages: 3674-86
  • Peer Reviewed
• [Journal Article] The RNA-binding protein HuD regulates autophagosome formation in pancreatic β cells by promoting autophagy-related gene 5 expression. (2014)
  • Author(s): Kim C, Kim W, Lee H, Ji E, Choe YJ, Martindale JL, Akamatsu W, Okano H, Kim HS, Nam SW, Gorospe M, Lee EK.
  • Journal Title: J Biol Chem. Volume: 289 Issue: 1 Pages: 112-121
  • DOI: 10.1074/jbc.m113.474700
  • Peer Reviewed
• [Journal Article] Increased l1 retrotransposition in the neuroral genome in schizophrenia. (2014)
  • Author(s): Miki Bundo, Manabu Toyoshima, Yohei Okada, Wado Akamatsu, Junko Ueda, Taeko Nemoto-Miyauchi, Fumiko Sunaga, Michihiro Toritsuka, Daisuke Ikawa, Akiyoshi Kakita, Motoichiro Kato, Kiyoto Kasai, Toshifumi Kishimoto, Hiroyuki Nawa, Hideyuki Okano, Takeo Yoshikawa, Tadafumi Katoemail, Kazuya Iwamoto
  • Journal Title: Neuron Volume: 81 Issue: 2 Pages: 306-313
  • DOI: 10.1016/j.neuron.2013.10.053
  • Peer Reviewed
• [Journal Article] Prenatal Deletion of the RNA-Binding Protein HuD Disrupts Postnatal Cortical Circuit Maturation and Behavior. (2014)
  • Author(s): Deboer EM, Azevedo R, Vega TA, Brodkin J, Akamatsu W, Okano H, Wagner GC, Rasin MR.
  • Journal Title: J Neurosci. Volume: 34 Issue: 10 Pages: 3674-3686
  • DOI: 10.1523/jneurosci.3703-13.2014
  • Peer Reviewed
• [Journal Article] A human Dravet syndrome model from patient induced pluripotent stem cells. (2013)
  • Author(s): Higurashi N, Uchida T, Lossin C, Misumi Y, Okada Y, Akamatsu W, Imaizumi Y, Zhang B, Nabeshima K, Mori MX, Katsurabayashi S, Shirasaka Y, Okano H, Hirose S.
  • Journal Title: Mol Brain Volume: 6 Issue: 1 Pages: 19-19
  • DOI: 10.1186/1756-6606-6-19
  • Peer Reviewed
• [Journal Article] Generation of human melanocytes from induced pluripotent stem cells. (2013)
  • Author(s): Ohta S, Imaizumi Y, Akamatsu W, Okano H, Kawakami Y.
  • Journal Title: Methods Mol Biol. Volume: 989 Pages: 193-215
  • DOI: 10.1007/978-1-62703-330-5_16
  • ISBN: 9781627033299, 9781627033305
  • Peer Reviewed
• [Journal Article] Enhanced aggregation of androgen receptor in induced pluripotent stem cell-derived neurons from spinal and bulbar muscular atrophy. (2013)
  • Author(s): Nihei Y, Ito D, Okada Y, Akamatsu W, Yagi T, Yoshizaki T, Okano H, Suzuki N.
  • Journal Title: J Biol Chem. Volume: 288 Issue: 12 Pages: 8043-8052
  • DOI: 10.1074/jbc.m112.408211
  • Peer Reviewed
• [Journal Article] Human induced pluripotent stem cell-derived ectodermal precursor cells contribute to hair follicle morphogenesis in vivo (2013)
  • Author(s): Veraitch O, Kobayashi T, Imaizumi Y, Akamatsu W, Sasaki T, Yamanaka S, Amagai M, Okano H and Ohyama M
  • Journal Title: J Invest Dermatol
  • Peer Reviewed
• [Journal Article] Human induced pluripotent stem cell-derived ectodermal precursor cells contribute to hair follicle morphogenesis in vivo. (2013)
  • Author(s): Veraitch O, Kobayashi T, Imaizumi Y, Akamatsu W, Sasaki T, Yamanaka S, Amagai M, Okano H and Ohyama M
  • Journal Title: J Invest Dermatol. Volume: - Issue: 6 Pages: 1479-1488
  • DOI: 10.1038/jid.2013.7
  • Peer Reviewed
• [Journal Article] 疾患特異的iPS細胞研究の基礎と実際 (2013)
  • Author(s): 赤松 和土
  • Journal Title: バイオクリニカ Volume: 28 Pages: 22-26
• [Journal Article] 神経系のiPS technologyの今後の展望 (2013)
  • Author(s): 赤松 和土
  • Journal Title: モダンフィジシャン Volume: 33 Pages: 696-698
• [Journal Article] Mitochondrial dysfunction associated with increased oxidative stress and -synuclein accumulation in PARK2 iPSC-derived neurons and postmortem brain tissue. (2012)
  • Author(s): Imaizumi Y
  • Journal Title: Mol Brain Volume: 5 Issue: 1 Pages: 35-35
  • DOI: 10.1186/1756-6606-5-35
  • Peer Reviewed
• [Journal Article] Regeneration of the damaged central nervous system through reprog ramming technology : Basic concepts and potential application for cell replacement therapy (2012)
  • Author(s): Matsui T, Akamatsu W, Nakamura M, Okano H
  • Journal Title: Exp Neurol
  • Peer Reviewed
• [Journal Article] Derivation of induced pluripotent stem cells by retroviral gene transduction in Mammalian species (2012)
  • Author(s): Imamura, M.
  • Journal Title: Methods Mol Biol Volume: 925 Pages: 21-48
  • DOI: 10.1007/978-1-62703-011-3_2
  • ISBN: 9781627030106, 9781627030113
  • Peer Reviewed
• [Journal Article] Establishment of induced pluripotent stem cells from centenarians for neurodegenerative disease research (2012)
  • Author(s): Yagi, T.
  • Journal Title: PLoS ONE Volume: 7 Issue: 7 Pages: e41572-e41572
  • DOI: 10.1371/journal.pone.0041572
  • Peer Reviewed
• [Journal Article] Neural Stem Cells Directly Differentiated from Partially Reprogrammed Fibroblasts Rapidly Acquire Gliogenic Competency (2012)
  • Author(s): Matsui T, Takano M, Yoshida K, Ono S, Fujisaki C, Matsuzaki Y, Toyama Y, Nakamura M, Okano H, Akamatsu W
  • Journal Title: Stem cells Volume: (In press) Issue: 6 Pages: 1109-1119
  • DOI: 10.1002/stem.1091
  • Peer Reviewed
• [Journal Article] RNA-binding protein HuD controls insulin translation (2012)
  • Author(s): Lee EK, Kim W, Tominaga K, Martindale JL, Yang X, Subaran SS, Carlson OD, Mercken EM, Kulkarni RN, Akamatsu W, Okano H, Perrone-Bizzozero NI, de Cabo R, Egan JM, Gorospe M
  • Journal Title: Mol Cell Volume: 45 (6) Issue: 6 Pages: 826-35
  • DOI: 10.1016/j.molcel.2012.01.016
  • Peer Reviewed
• [Journal Article] Regeneration of the damaged central nervous system through reprogramming technology: Basic concepts and potential application for cell replacement therapy. (2012)
  • Author(s): Matsui T, Akamatsu W, Nakamura M, Okano H.
  • Journal Title: Exp Neurol. Volume: 00 Pages: 0-0
  • DOI: 10.1016/j.expneurol.2012.09.016
  • Peer Reviewed
• [Journal Article] RNA-Binding Protein HuD Controls Insulin Translation (2012)
  • Author(s): Lee EK, Kim W, Tominaga K, Martindale JL, Yang X, Subaran SS, Carlson OD, Mercken EM, Kulkarni RN, Akamatsu W, Okano H, Perrone-Bizzozero NI, de Cabo R, Egan JM, Gorospe M.
  • Journal Title: Molecular Cell Volume: 45(6) Pages: 826-35
  • Peer Reviewed
• [Journal Article] Modeling familial Alzheimer's disease with induced pluripotentstem cells (2011)
  • Author(s): Yagi T, Ito D, Okada Y, Akamatsu W, Nihei Y, Yoshizaki T, Yamanaka S, Ok ano H, Suzuki N
  • Journal Title: Hum Mol Genet Volume: 20(23) Pages: 4530-9
  • Peer Reviewed
• [Journal Article] Modeling familial Alzheimer's disease with induced pluripotent stem cells. (2011)
  • Author(s): Yagi T, Ito D, Okada Y, Akamatsu W, Nihei Y, Yoshizaki T, Yamanaka S, Okano H, Suzuki N
  • Journal Title: Human Molecular Genetics Volume: 20(23) Pages: 4530-9
  • NAID: 130004505083
  • Peer Reviewed
• [Presentation] 多能性幹細胞(ES細胞/iPS細胞)を用いた神経疾患の再生医療と病態研究 (2014)
  • Author(s): 赤松和土
  • Organizer: 順天堂大学第136回お茶の水木曜会
  • Place of Presentation: 東京
  • Year and Date: 2014-03-13
  • Invited
• [Presentation] Direct Reprogrammingの最近の進歩:神経幹細胞の直接誘導とその応用 (2014)
  • Author(s): 赤松和土
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都(シンポジウム)
  • Year and Date: 2014-03-05
  • Invited
• [Presentation] iPS細胞技術を用いた神経疾患研究と治療 (2013)
  • Author(s): 赤松和土
  • Organizer: 第37回日本血液事業学会総会
  • Place of Presentation: 札幌(シンポジウム)
  • Year and Date: 2013-10-21
  • Invited
• [Presentation] iPS technology-based regenerative medicine for damaged central nervous system (2013)
  • Author(s): 赤松和土
  • Organizer: 第11回遺伝子治療学会
  • Place of Presentation: 岡山(シンポジウム)
  • Year and Date: 2013-07-06
  • Invited
• [Presentation] 疾患iPS細胞と創薬:「神経疾患患者由来細胞からの神経系細胞の誘導と病態解析」 (2013)
  • Author(s): 赤松和土
  • Organizer: 炎症再生学会
  • Place of Presentation: 京都(シンポジウム)
  • Year and Date: 2013-07-02
  • Invited
• [Presentation] iPS細胞を使った神経疾患の治療法の開発 (2013)
  • Author(s): 赤松和土
  • Organizer: 第20回東京血管疾患研究所セミナー
  • Place of Presentation: 東京
  • Year and Date: 2013-06-08
  • Invited
• [Presentation] iPS細胞技術を用いた神経系の再生医療と疾患解析 (2013)
  • Author(s): 赤松和土
  • Organizer: 第2回小児泌尿器科研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-06-01
  • Invited
• [Presentation] 多能性幹細胞を用いた神経疾患の再生医療と病態研究 (2013)
  • Author(s): 赤松和土
  • Organizer: 第11回横浜小児先端医療セミナー
  • Place of Presentation: 横浜
  • Year and Date: 2013-05-24
  • Invited
• [Presentation] iPS細胞技術の神経疾患研究・治療への応用 (2013)
  • Author(s): 赤松和土
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島
  • Year and Date: 2013-04-19
  • Invited
• [Presentation] 45 iPS細胞技術を用いた中枢神経系の再生と創薬研究:iPS technology-based cell therapy for damaged CNS and investigation of neural disorders (2013)
  • Author(s): 赤松和土,岡野栄之
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京(シンポジウム)
  • Year and Date: 2013-03-29
  • Invited
• [Presentation] 疾患特異的iPS細胞を用いた病態解明および治療法確立研究:神経疾患患者由来細胞からの神経系細胞の誘導と病態解析 (2013)
  • Author(s): 赤松和土
  • Organizer: 日本再生医療学会総会
  • Place of Presentation: 東京(シンポジウム)
  • Year and Date: 2013-03-22
  • Invited
• [Presentation] 多能性幹細胞・神経幹細胞を用いた再生医療と病態解析 (2013)
  • Author(s): 赤松和土
  • Organizer: 愛知医科大学細胞治療研究会
  • Place of Presentation: 愛知
  • Year and Date: 2013-03-05
  • Invited
• [Presentation] ALSに対する再生医療の開発:幹細胞生物学を応用した神経疾患病態研究 (2012)
  • Author(s): 赤松和土
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2012-05-23
  • Invited
• [Presentation] 多能性幹細胞から神経幹細胞を生み出す分子機構とその応用 (2012)
  • Author(s): 赤松和土
  • Organizer: 第12回日本分子生物学会春季シンポジウム
  • Place of Presentation: 山梨
  • Year and Date: 2012-04-26
  • Invited
• [Presentation] 13基礎研究セミナー:多能性幹細胞由来神経幹細胞を用いた神経系の再生医療の展望 (2012)
  • Author(s): 赤松和土
  • Organizer: 第116回日本眼科学会
  • Place of Presentation: 東京(シンポジウム)
  • Year and Date: 2012-04-06
  • Invited
• [Presentation] "ヒト"をキーワードにした多能性幹細胞研究の展開:体細胞からの安全な神経幹細胞の直接誘導 (2012)
  • Author(s): 赤松和土
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 長野(シンポジストおよび座長)
  • Year and Date: 2012-03-31
  • Invited
• [Presentation] 体細胞からの安全な神経幹細胞の直接誘導 (2012)
  • Author(s): 赤松和土
  • Organizer: 第89回日本生理学会大会・企画シンポジウム(招待講演)
  • Place of Presentation: 松本文化会館・長野
• [Presentation] 多能性幹細胞を用いた神経系の再生医療の展望 (2011)
  • Author(s): 赤松和土,岡野栄之
  • Organizer: 長野県医学会例会
  • Place of Presentation: 長野(特別講演)
  • Year and Date: 2011-07-25
• [Presentation] iPS細胞技術の神経疾患研究・治療への応用
  • Author(s): 赤松 和土, 岡野 栄之
  • Organizer: 第116回日本小児科学会学術集会
  • Place of Presentation: 広島
  • Invited
• [Presentation] 多能性幹細胞を用いた神経疾患の再生医療と病態研究
  • Author(s): 赤松 和土
  • Organizer: 第11回横浜小児先端医療セミナー
  • Place of Presentation: 横浜
  • Invited
• [Presentation] iPS細胞技術を用いた神経系の再生医療と疾患解析
  • Author(s): 赤松 和土
  • Organizer: 第2回小児泌尿器科研究会
  • Place of Presentation: 東京
  • Invited
• [Presentation] iPS細胞を使った神経疾患の治療法の開発
  • Author(s): 赤松 和土
  • Organizer: 第20回東京血管疾患研究所セミナー
  • Place of Presentation: 東京
  • Invited
• [Presentation] iPS technology-based regenerative medicine for damaged central nervous system
  • Author(s): 赤松 和土
  • Organizer: 第11回遺伝子治療学会
  • Place of Presentation: 岡山
  • Invited
• [Presentation] iPS 細胞技術を用いた神経疾患研究と治療
  • Author(s): 赤松 和土
  • Organizer: 第37 回日本血液事業学会総会
  • Place of Presentation: 札幌
  • Invited
• [Presentation] Direct Reprogrammingの最近の進歩：神経幹細胞の直接誘導とその応用
  • Author(s): 赤松 和土
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 多能性幹細胞(ES細胞/iPS細胞）を用いた神経疾患の再生医療と病態研究
  • Author(s): 赤松 和土
  • Organizer: 順天堂大学第136回お茶の水木曜会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 多能性幹細胞由来神経幹細胞を用いた神経系の再生医療の展望
  • Author(s): 赤松 和土
  • Organizer: 第116回日本眼科学会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 多能性幹細胞から神経幹細胞を生み出す分子機構とその応用
  • Author(s): 赤松 和土
  • Organizer: 第12回日本分子生物学会春季シンポジウム
  • Place of Presentation: 山梨
  • Invited
• [Presentation] 幹細胞生物学を応用した神経疾患病態研究
  • Author(s): 赤松 和土
  • Organizer: 第53回日本神経学会学術大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 神経疾患患者由来細胞からの神経系細胞の誘導と病態解析
  • Author(s): 赤松 和土
  • Organizer: 日本再生医療学会総会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] PS細胞技術を用いた中枢神経系の再生と創薬研究
  • Author(s): 赤松 和土, 岡野 栄之
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Invited
• [Patent(Industrial Property Rights)] 神経幹細胞製造方法 (2009)
  • Inventor(s): 岡野栄之、赤松和土
  • Industrial Property Rights Holder: 岡野栄之、赤松和土
  • Industrial Property Rights Type: 特許
  • Filing Date: 2009-11-04
  • Overseas