Disease mechanism research using cellular amyotrophic lateral sclerosis models derived from hES cells

• Project/Area Number: 23500446
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kyoto University
• Principal Investigator: AIBA Kazuhiro 京都大学, 物質-細胞統合システム拠点, 准教授 (30564752)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 筋萎縮性側索硬化症 / 脳神経疾患 / ヒトES細胞 / ヒト多能性幹細胞 / 疾患モデル細胞

Research Abstract

Overexpression of SOD1, a responsible gene of amyotrophic lateral sclerosis (ALS) did not affect differentiation of motor neuron and astrocyte from human embryonic stem cells. But we found that one mutant type of SOD1 affected the length of neuritis. In future, we will investigate whether this change is involved in the onset or progress of ALS.

Research Products

• [Journal Article] A chemical probe that labels human pluripotent stem cells (2014)
  • Author(s): Hirata N, Nakagawa M, Fujibayashi Y, Yamauchi K, Murata A, Minami I, Tomioka M, Kondo T, Kuo TF, Endo H, Inoue H, Sato S, Ando S, Kawazoe Y, Aiba K, Nagata K, Kawase E, Chang YT, Suemori H, Eto K, Nakauchi H, Yamanaka S, Nakatsuji N, Ueda K, Uesugi M
  • Journal Title: Cell reports Volume: 6 Issue: 6 Pages: 1165-74
  • DOI: 10.1016/j.celrep.2014.02.006
  • NAID: 120005466668
  • Peer Reviewed / Open Access
• [Journal Article] Multidisciplinary Research of Human Pluripotent Stem Cells for Application to Cell Therapy and Drug Discovery (2013)
  • Author(s): Norio Nakatsuji, Eihachiro Kawase, Takamichi Miyazaki, Itsunari Minami and Kazuhiro Aiba
  • Journal Title: Tissue Engineering and Regenerative Medicine Volume: 10 Issue: 4 Pages: 160-163
  • DOI: 10.1007/s13770-013-0019-y
• [Journal Article] Amyotrophic Lateral Sclerosis Model Derived from Human Embryonic Stem Cells Overexpressing Mutant Superoxide Dismutase 1 (2012)
  • Author(s): Wada T, Goparaju SK, Tooi N, Inoue H, Takahashi R, Nakatsuji N, Aiba K
  • Journal Title: Stem Cells Trans Med Volume: 1 Issue: 5 Pages: 396-402
  • DOI: 10.5966/sctm.2011-0061
  • Peer Reviewed
• [Journal Article] A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions (2012)
  • Author(s): Minami I, Yamada K, Otsuji TG, Yamamoto T, Shen Y, Otsuka S, Kadota S, Morone N, Barve M, Asai Y, Tenkova-Heuser T, Heuser JE, Uesugi M, Aiba K, Nakatsuji N
  • Journal Title: Cell Rep Volume: 2(5) Issue: 5 Pages: 1448-60
  • DOI: 10.1016/j.celrep.2012.09.015
  • Peer Reviewed
• [Journal Article] Chemical Library Screening Identifies a Small Molecule That Downregulates SOD1 Transcription for Drugs to Treat Amyotrophic Lateral Sclerosis (2011)
  • Author(s): Murakami, G.; Inoue, H.; Tsukita, K.; Asai, Y.; Amagai, Y.; Aiba, K.; Shimogawa, H.; Uesugi, M.; Nakatsuji, N.; Takahashi, R
  • Journal Title: Journal of Biomolecular Screening Volume: 16 Issue: 4 Pages: 405-414
  • DOI: 10.1177/1087057110397888
  • NAID: 120004225661
  • Peer Reviewed
• [Journal Article] Efficient and Accurate Homologous Recombination in hESCs and hiPSCs Using Helper-dependent Adenoviral Vectors (2011)
  • Author(s): Aizawa E, Hirabayashi Y, Iwanaga Y, Suzuki K, Sakurai K, Shimoji M, Aiba K, Wada T, Tooi N, Kawase E, Suemori H, Nakatsuji N, Mitani K
  • Journal Title: Mol Ther Volume: 6 Issue: 2 Pages: 424-431
  • DOI: 10.1038/mt.2011.266
  • Peer Reviewed
• [Journal Article] ES細胞（胚性幹細胞）研究 (2011)
  • Author(s): 門田真、饗庭一博、 中辻憲夫
  • Journal Title: 日本臨牀 幹細胞治療―基礎研究の進歩と臨床応用― Volume: 69 Pages: 2109-2113
• [Presentation] 遺伝子改変ヒトES 細胞由来ALS-SOD1 モデル細胞の作製および解析 (2014)
  • Author(s): 磯部武久, 遠井紀江, 中辻憲夫, 饗庭一博
  • Organizer: 日本薬学会第134回年会
  • Place of Presentation: 熊本県熊本市
  • Year and Date: 2014-03-30
• [Presentation] 遺伝子改変ヒトES細胞由来ALS-SOD1モデル細胞の作製および解析 (2014)
  • Author(s): 磯部武久、遠井紀江、中辻憲夫、饗庭一博
  • Organizer: 日本薬学会第134回年会
  • Place of Presentation: 熊本県、熊本市
• [Presentation] 遺伝子改変ヒトES 細胞由来ALS モデル細胞の作製および病態解析 (2013)
  • Author(s): 磯部武久, 遠井紀江, 饗庭一博, 中辻憲夫
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2013-12-04
• [Presentation] Amyotrophic lateral sclerosis model cells derived from human embryonic stem cells overexpressing mutant SOD1 or TDP-43 (2013)
  • Author(s): Isobe T, Tooi N, Aiba K, Nakatsuji N
  • Organizer: ISSCR 11th Annual meeting
  • Place of Presentation: アメリカ合衆国ボストン
  • Year and Date: 2013-06-13
• [Presentation] Amyotrophic lateral sclerosis model cells derived from human embryonic stem cells overexpressing mutant SOD1 or TDP-43 (2013)
  • Author(s): Isobe T, Tooi N, Aiba K, Nakatsuji N
  • Organizer: ISSCR 11th Annual meeting
  • Place of Presentation: アメリカ合衆国、ボストン
• [Presentation] 遺伝子改変ヒトES細胞由来ALSモデル細胞の作製および病態解析 (2013)
  • Author(s): 磯部武久、遠井紀江、饗庭一博、中辻憲夫
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 兵庫県、神戸市
• [Presentation] Site-directed integration of transgenes and human pluripotent stem cell-derived neurodegenerative disease models (2013)
  • Author(s): Kazuhiro Aiba
  • Organizer: University System of Taiwan-iCeMS Joint Symposium
  • Place of Presentation: 京都府、京都市
  • Invited
• [Presentation] AMYOTROPHIC LATERAL SCLEROSIS MODEL CELLS DERIVED FROM HUMAN EMBRYONIC STEM CELLS OVEREXPRESSING MUTANT SOD1 or TDP-43 (2013)
  • Author(s): Takehisa Isobe, Norie Tooi, Kazuhiro Aiba and Norio Nakatsuji
  • Organizer: ISSCR 11th Annual Meeting
  • Place of Presentation: Boston, USA
• [Presentation] Cellular neurodegenerative disease models derived from genetically manipulated human pluripotent stem cells (2013)
  • Author(s): Kazuhiro Aiba, Sravan K. Goparaju, Norie Tooi, Itsunari Minami, Norio Nakatsuji
  • Organizer: RSC pubulishing-iCeMS Joint international Symposium
  • Place of Presentation: 京都市、京都府
• [Presentation] Development of a human embryonic stem cell-based disease model for amyotrophic lateral sclerosis (2013)
  • Author(s): Sravan K. Goparaju, Tamaki Wada, Norie Tooi, Kazuhiro Aiba, Norio Nakatsuji
  • Organizer: RSC pubulishing-iCeMS Joint international Symposium
  • Place of Presentation: 京都市、京都府
• [Presentation] Site-directed integration of transgenes and human pluripotent stem cell-derived neurodegenerative disease models (2012)
  • Author(s): Aiba K
  • Organizer: Using Stem Cells for Biological and Therapeutical Discovery in Mental Illness
  • Place of Presentation: アメリカ合衆国ベセスダ
  • Year and Date: 2012-04-25
• [Presentation] ヒト多能性幹細胞から作製されるモデル細胞-神経変性疾患モデルと心筋モデル- (2012)
  • Author(s): 饗庭一博
  • Organizer: 日本農芸化学会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2012-03-23
• [Presentation] Cellular neurodegenerative disease models derived from genetically manipulated human pluripotent stem cells (2012)
  • Author(s): Aiba K, Honda M, Goparaju SK, Tooi N, Minami I, Nakatsuji N
  • Organizer: ISSCR 10th Annual Meeting
  • Place of Presentation: 神奈川県横浜市
• [Presentation] Development of a human embryonic stem cell-based disease model for amyotrophic lateral sclerosis (2012)
  • Author(s): Goparaju SK, Wada T, Tooi N, Aiba K, Nakatsuji N
  • Organizer: ISSCR 10th Annual Meeting
  • Place of Presentation: 神奈川県横浜市
• [Presentation] Chemical library screening identifies a small molecule that downregulates SOD1 transcription for drugs to treat amyotrophic lateral sclerosis (2012)
  • Author(s): Murakami G, Inoue H, Asai Y, Aiba K, Itoh H, Uesugi M, Nakatsuji N, Takahashi R
  • Organizer: 13th Asian Oceanian Congress of Neurology
  • Place of Presentation: オーストラリア メルボルン
• [Presentation] Development of a human embryonic stem cell-based disease model for amyotrophic lateral sclerosis (2012)
  • Author(s): Sravan K. Goparaju, Tamaki Wada, Norie Tooi, Kazuhiro Aiba, Norio Nakatsuji
  • Organizer: Crossing Boundaries: Stem Cells, Materials, Mesoscopic Sciences and Beyond
  • Place of Presentation: 北京市、中国
• [Presentation] Site-directed integration of transgenes and human pluripotent stem cell-derived neurodegenerative disease models (2012)
  • Author(s): Kazuhiro Aiba
  • Organizer: Using Stem Cells for Biological and Therapeutics Discovery in Mental Illness
  • Place of Presentation: Bethesda, USA
  • Invited
• [Presentation] Chemical library screening identifies a small molecule that downregulates SOD1 transcription for drugs to treat amyotrophic lateral sclerosis (2012)
  • Author(s): Gaku Murakami, Haruhisa Inoue, Yasuyuki Asai, Kazuhiro Aiba, Hideaki Itoh, Motonari Uesugi, Norio Nakatsuji, Ryosuke Takahashi
  • Organizer: 13th Asian Oceanian Congress of Neurology
  • Place of Presentation: Melbourne, Australia
• [Presentation] CELLULAR NEURODEGENERATIVE DISEASE MODELS DERIVED FROM GENETICALLY MANIPULATED HUMAN PLURIPOTENT STEM CELLS (2012)
  • Author(s): Kazuhiro Aiba, Makoto Honda, Sravan K. Goparaju, Norie Tooi, Itsunari Minami, Norio Nakatsuji
  • Organizer: ISSCR 10th Annual Meeting
  • Place of Presentation: 横浜市、神奈川県
• [Presentation] Development of a human embryonic stem cell-based disease model for amyotrophic lateral sclerosis (2012)
  • Author(s): Sravan K. Goparaju, Tamaki Wada, Norie Tooi, Kazuhiro Aiba, Norio Nakatsuji
  • Organizer: ISSCR 10th Annual Meeting
  • Place of Presentation: 横浜市、神奈川県
• [Presentation] SOD1転写を標的とした家族性筋萎縮性側索硬化症の新規治療薬開発 (2012)
  • Author(s): Gaku Murakami, Haruhisa Inoue, Kayoko Tsukita, Yasuyuki Asai, Kazuhiro Aiba, Yuji Amagai, Hiroki Shimogawa, Motonari Uesugi, Norio Nakatsuji, Ryosuke Takahashi
  • Organizer: 第35回日本神経科学大会
  • Place of Presentation: 名古屋市、愛知県
• [Presentation] ヒト多能性幹細胞から作製されるモデル細胞 －神経変性疾患モデルと心筋モデル－ (2012)
  • Author(s): 饗庭一博
  • Organizer: 日本農芸化学会(招待講演)
  • Place of Presentation: 京都女子大学（京都府）
• [Presentation] 疾患発症機序と創薬研究のためのヒト多能性幹細胞由来の神経変性疾患モデル細胞 (2011)
  • Author(s): 饗庭一博
  • Organizer: ヒトES/iPS細胞：産業応用最前線セミナー ～細胞治療と創薬スクリーニング～(招待講演)
  • Place of Presentation: 東京コンファレンスセンター・品川（東京都）
• [Presentation] Human pluripotent stem cells and in vitro disease models (2011)
  • Author(s): Kazuhiro Aiba
  • Organizer: ABC 2011 in Kyoto - ABC proteins/Membrane Meso-Domains/ES-iPS Cells-(招待講演)
  • Place of Presentation: 京都大学（京都府）
• [Book] Cre/loxP, Flp/FRT systems and pluripotent stem cell lines. In Site-directed insertion of transgenes (2012)
  • Author(s): Tahimic CGT, Sakurai K, Aiba K, and Nakatsuji N
  • Publisher: Springer
• [Book] カラー版内科 幹細胞を用いた薬効評価 (2012)
  • Author(s): 門田真、饗庭一博、中辻憲夫
  • Publisher: 西村書店
• [Book] Efficient integration of transgenes and their reliable expression in human embryonic stem cells In Embryonic Stem Cells: Basic Biology to Bioengineering (2011)
  • Author(s): Sakurai K, Shimoji M, Aiba K, and Nakatsuji N
  • Publisher: INTECH
• [Remarks] ホームページ
  • URL: http://www.icems.kyoto-u.ac.jp/j/ppl/grp/nakatsuji.html
• [Remarks] ヒトES 細胞からALS 疾患モデルを作製し, 病状再現に成功, NHK(5月9日, 10日), 京都新聞(5月9日 1面), 産経新聞(5月9日 2面), 読売新聞(5月9日 33 面), 朝日新聞(5月9日 夕刊 8面),日本経済新聞(5月9日 34面),日刊工業新聞(5月9日 19 面), Wall Street Journal日本版(2012年5月9日 web), その他 (2012年5月) (報道)
  • URL: http://www.icems.kyoto-u.ac.jp/j/pr/2012/05/09-nr.html