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Study on molecular regulation of muscle regeneration by mesenchymal cells

Research Project

Project/Area Number 20590418
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

SUZUKI Yuko  National Center of Neurology and Psychiatry, 神経研究所・遺伝子疾患治療研究部, 室長 (00342931)

Co-Investigator(Kenkyū-buntansha) TAKEDA Shin'ichi  独)国立精神・神経医療研究センター, 神経研究所・遺伝子疾患治療研究部, 部長 (90171644)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords骨格筋 / 筋再生 / 筋ジストロフィー / 細胞移植 / 幹細胞 / 筋芽細胞 / Side Population細胞 / CD248 / 細胞老化 / 筋衛星細胞 / SP細胞 / 骨格筋間葉系細胞
Research Abstract

We found that CD31(-) CD45(-) side population (SP) cells in skeletal muscle are activated during muscle regeneration and promote the proliferation and the migration of grafted myoblasts. To further clarify the roles for CD31(-) CD45(-) SP cells, we generated CD248-sDTR-EGFP transgenic mice. However, the mice did not express sDTR-EGFP. This could be because the 1.0 kb upstream sequences of the CD248 gene were not enough to drive the expression of the reporter gene. We next analyzed the genome-wide gene expression pattern of mesenchymal cells (a descendent of CD31(-) CD45(-) SP cells) from dystrophin-deficient mice of different age. We found that mesenchymal cells in mdx mice experience cell senescence and immune response- and defense-related genes. These findings suggest that impaired muscle regeneration seen in advanced dystrophic muscle can be partly explained by exhausted mesenchymal cells, which otherwise promote muscle regeneration.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (51 results)

All 2011 2010 2009 2008 Other

All Journal Article (31 results) (of which Peer Reviewed: 29 results) Presentation (8 results) Book (11 results) Remarks (1 results)

  • [Journal Article] Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle2011

    • Author(s)
      Shimizu N, Yoshikawa N, Ito N, Maruyama T, Suzuki Y, Takeda S, Nakae J, Tagata Y, Nishitani S, Takehana K, Sano M, Fukuda K, Suematsu M, Morimoto C, Tanaka H
    • Journal Title

      Cell Metabolism 13(2)

      Pages: 170-82

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reactive gliosis of astrocytes and Muller glial cells in retina of POMGnT1-deficient mice2011

    • Author(s)
      Takahashi H, Kanesaki H, Igarashi T, Kameya S, Yamaki K, Mizota A, Kudo A, Miyagoe-Suzuki Y, Takeda S, Takahashi H
    • Journal Title

      Molecular and Cellular Neuroscience 47(2)

      Pages: 119-30

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle.2011

    • Author(s)
      Shimizu N, Yoshikawa N, Ito N, Maruyama T, Suzuki Y, Takeda S, Nakae J, Tagata Y, Nishitani S, Takehana K, Sano M, Fukuda K, Suematsu M, Morimoto C, Tanaka H
    • Journal Title

      Cell Metabolism

      Volume: 13 Pages: 170-182

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic background affects properties of satellite cells and mdx phenotypes2010

    • Author(s)
      Fukada S, Morikawa D, Yamamoto Y, Yoshida T, Sumie N, Yamaguchi M, Ito T, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Yamamoto H
    • Journal Title

      Am J Pathol. 176(5)

      Pages: 2414-24

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gene therapy for muscle disease. Mini-review2010

    • Author(s)
      Miyagoe-Suzuki Y, Takeda S
    • Journal Title

      Exp.Cell Res.(Epub 2010 May 24. Review) 316(18)

      Pages: 3087-92

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Six family genes control the proliferation and differentiation of muscle satellite cells.2010

    • Author(s)
      Yajima H, Motohashi N, Ono Y, Sato S, Ikeda K, Masuda S, Yada E, Miyagoe-Suzuki Y, Takeda S, Kawakami K
    • Journal Title

      Exp.Cell Res. 316(17)

      Pages: 2932-44

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Post-translational maturation of dystroglycan is necessary for pikachurin binding and ribbon synaptic localization.2010

    • Author(s)
      Kanagawa M, Omori Y, Sato S, Kobayashi K, Miyagoe-Suzuki Y, Takeda S, Endo T, Furukawa T, Toda T
    • Journal Title

      J Biol Chem 285(41)

      Pages: 31208-16

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetic background affects properties of satellite cells and mdx phenotypes.2010

    • Author(s)
      Fukada S, Morikawa D, Yamamoto Y, Yoshida T, Sumie N, Yamaguchi M, Ito T, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Yamamoto H
    • Journal Title

      Am J Pathol

      Volume: 176 Pages: 2414-2424

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Six family genes control the proliferation and differentiation of muscle satellite cells.2010

    • Author(s)
      Yajima H, Motohashi N, Ono Y, Sato S, Ikeda K, Masuda S, Yada E, Miyagoe-Suzuki Y, Takeda S
    • Journal Title

      Exp Cell Res

      Volume: 316 Pages: 2932-2944

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Post-translational maturation of dystroglycan is necessary for pikachurin binding and ribbon synaptic localization.2010

    • Author(s)
      Kanagawa M, Omori Y, Sato S, Kobayashi K, Miyagoe-Suzuki Y, Takeda S, Endo T, Furukawa T, Toda T
    • Journal Title

      J Biol Chem

      Volume: 285 Pages: 31208-31216

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集再生医療-臨床応用へ向けての現状と課題「筋ジストロフィー」2010

    • Author(s)
      鈴木友子、武田伸一
    • Journal Title

      総合リハビリテーション

      Volume: 316 Pages: 25-29

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Gene therapy for muscle disease.2010

    • Author(s)
      Miyagoe-Suzuki Y, Takeda S
    • Journal Title

      Exp Cell Res

      Volume: 39 Pages: 3087-3092

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic Background Affects Properties of Satellite Cells and mdx Phenotypes2010

    • Author(s)
      Fukada SI, Morikawa D, Yamamoto Y, Yoshida T, Sumie N, Yamaguchi M, Ito T, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Yamamoto H.
    • Journal Title

      Am J Pathol. (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro.2009

    • Author(s)
      Miyagoe-Suzuki Y, Masubuchi N, Miyamoto K, Wada MR, Yuasa S, Saito F, Matsumura K, Kanesaki H, Kudo A, Manya H, Endo T, Takeda S
    • Journal Title

      Mech Dev. 126(3-4)

      Pages: 107-16

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy.2009

    • Author(s)
      Kanagawa M, Nishimoto A, Chiyonobu T, Takeda S, Miyagoe-Suzuki Y, Wang F, Fujikake N, Taniguchi M, Lu Z, Tachikawa M, Nagai Y, Tashiro F, Miyazaki J, Tajima Y, Takeda S, Endo T, Kobayashi K, Campbell KP, Toda T
    • Journal Title

      Hum Mol Genet. 18(4)

      Pages: 621-31

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells.2009

    • Author(s)
      Chang H, Yoshimoto M, Umeda K, Iwasa T, Mizuno Y, Fukada SI, Yamamoto H, Motohashi N, Miyagoe-Suzuki Y, Takeda S, Heike T, Nakahata T
    • Journal Title

      FASEB J. 23(6)

      Pages: 1907-19

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells2009

    • Author(s)
      Chang H, Yoshimoto M, Umeda K, Iwasa T, Mizuno Y, Fukada S, Yamamoto H, Motohashi N, Miyagoe-Suzuki Y, Takeda S, Heike T, Nakahata T
    • Journal Title

      FASEB J. 23

      Pages: 1907-1919

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 筋ジストロフィーに対する先端治療法の開発2009

    • Author(s)
      鈴木友子, 武田伸一
    • Journal Title

      ゲノム医学 9

      Pages: 195-198

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro2009

    • Author(s)
      Miyagoe-Suzuki Y, et al.
    • Journal Title

      Mechanisms of Development 126

      Pages: 107-116

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Residual laminin-binding activity and enhanced dystroglycan glycosylation by LARGE in novel model mice to dystroglycanopathy2009

    • Author(s)
      Kanagawa M, et al.
    • Journal Title

      Human Molecular Genetics 18

      Pages: 621-631

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells2009

    • Author(s)
      Chang H, et al.
    • Journal Title

      The FASEB Journal (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD90-positive cells, an additional cell population, produce laminin <alpha>2 upon transplantation to dy3k/dy3k mice.2008

    • Author(s)
      Fukada S, Yamamoto Y, Segawa M, Sakamoto K, Nakajima M, Sato M, Morikawa D, Uezumi A, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Yamamoto H
    • Journal Title

      Exp.Cell Res. 314

      Pages: 193-203

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recombinant Adeno-associated Virus Type 8-Mediated Extensive Therapeutic Gene Delivery into Skeletal Muscle of alpha-Sarcoglycan-Deficient Mice.2008

    • Author(s)
      Nishiyama A, Ampong BN, Ohshima S, Shin JH, Nakai H, Imamura M, Miyagoe-Suzuki Y, Okada T, Takeda S
    • Journal Title

      Hum Gene Ther 19

      Pages: 719-30

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Downstream utrophin enhancer is required for expression of utrophin in skeletal muscle.2008

    • Author(s)
      Tanihata J, Suzuki N, Miyagoe-Suzuki Y, Imaizumi K, Takeda S
    • Journal Title

      J Gene Med. 10

      Pages: 702-13

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Muscle CD31(-) CD45(-) side population cells promote muscle regeneration by stimulating proliferation and migration of myoblasts.2008

    • Author(s)
      Motohashi N, Uezumi A, Yada E, Fukada S, Fukushima K, Imaizumi K, Miyagoe-Suzuki Y, Takeda S
    • Journal Title

      Am J Pathol. 173

      Pages: 781-91

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis.2008

    • Author(s)
      Segawa M, Yamamoto Y, Yahagi H, Kanematsu M, Sato M, Ito T, Uezumi A, Hayashi S, Miyagoe-Suzuki Y, Takeda S, Tsujikawa K, Yamamoto H
    • Journal Title

      Exp.Cell Res. 314(17)

      Pages: 3232-44

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recombinant Adeno-associated Virus Type 8-Mediated Extensive Therapeutic Gene Delivery into Skeletal Muscle of alpha-Sarcoglycan-Deficient Mice2008

    • Author(s)
      Nishiyama A, et al.
    • Journal Title

      Human Gene Therapy 19

      Pages: 719-730

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downstream utrophin enhancer is required for expression of utrophin in skeletal muscle2008

    • Author(s)
      Tanihata J, et al.
    • Journal Title

      Journal of Gene Medicine 10

      Pages: 702-713

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Muscle CD31(-) CD45(-) side population cells promote muscle regeneration by stimulating proliferation and migration of myoblasts2008

    • Author(s)
      Motohashi N, et al.
    • Journal Title

      American Journal of Pathology 173

      Pages: 781-791

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis2008

    • Author(s)
      Segawa M, et al.
    • Journal Title

      Experimental Cell Research 314

      Pages: 3232-3244

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reactive gliosis of astrocytes and Muller glial cells in retina of POMGnT1-deficient mice.

    • Author(s)
      Takahashi H, Kanesaki H, Igarashi T, Kameya S, Yamaki K, Mizota A, Kudo A, Miyagoe-Suzuki Y, Takeda S, Takahashi H
    • Journal Title

      Mol Cell Neurosc

      Volume: 印刷中

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 遺伝性筋疾患への幹細胞移植治療の基盤研究2010

    • Author(s)
      鈴木友子
    • Organizer
      第25回日本整形外科学会基礎学術集会シンポジウム6臨床への橋渡し研究の現状-3腱・靭帯・筋肉
    • Place of Presentation
      京都
    • Year and Date
      2010-10-15
    • Related Report
      2010 Final Research Report
  • [Presentation] 遺伝性筋疾患への幹細胞移植治療の基盤研究2010

    • Author(s)
      鈴木友子
    • Organizer
      第25回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2010-10-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] nNOS regulates skeletal muscle mass2009

    • Author(s)
      鈴木友子、武田伸一
    • Organizer
      第32回分子生物学会ワークショップ 2W8-4
    • Place of Presentation
      パシフィコ 横浜会議センター 第8会場(横浜)
    • Year and Date
      2009-12-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] 「神経型一酸化窒素合成酵素(nNOS)は骨格筋の可塑性の制御因子である2009

    • Author(s)
      鈴木友子、伊藤尚基、武田伸一、鈴木直輝
    • Organizer
      第17回日本運動生理学会大会シンポジウムV「骨格筋の可塑性」
    • Place of Presentation
      東京慈恵会医科大学西新橋校
    • Year and Date
      2009-07-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 神経型一酸化窒素合成酵素(nNOS)は骨格筋の可塑性の制御因子である2009

    • Author(s)
      鈴木友子, 伊藤尚基, 武田伸一, 鈴木直輝
    • Organizer
      第17回日本運動生理学会大会
    • Place of Presentation
      東京慈恵会医科大学(東京都港区西新宿)
    • Year and Date
      2009-07-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] Making muscle from induced pluripotent stem(iPS)cells2009

    • Author(s)
      Miyagoe-Suzuki Y, Motohashi N, Yada E, Segawa M, Wang B, Harano C, Masuda S, Yoshida M, Takeda S
    • Organizer
      Eighth French-Japanese workshop on muscular dystrophies
    • Place of Presentation
      サルペトリエール病院(フランス、パリ)
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Making muscle from induced pluripotent stem (iPS) cells. Institute de Myologie, Hopital de la Salpetriere, Paris2009

    • Author(s)
      Yuko Suzuki, Norio Motohashi, Erica Yada, Makoto Segawa, Wang Bo, Chika Harano, Satoru Masuda, Mikiharu Yoshida, Shin'ichi Takeda
    • Organizer
      第8回仏日筋ジストロフィーシンポジウム-病態から生物学的治療法へ-
    • Related Report
      2010 Final Research Report
  • [Presentation] Abnormal glycosylation of alpha-dystroglycan results in poor proliferation and limited migration of muscle satellite cells2008

    • Author(s)
      Yuko Miyagoe-Suzuki, et al.
    • Organizer
      6^<th> International Society for Stem Cell Research Annual Meeting 2008
    • Place of Presentation
      Pennsylvania Convention Center, Philadelphia
    • Year and Date
      2008-06-11
    • Related Report
      2008 Annual Research Report
  • [Book] 生物機能モデルと新しいリソース・リサーチツール2011

    • Author(s)
      鈴木友子、遠藤玉夫
    • Total Pages
      671
    • Publisher
      エル・アイ・シー
    • Related Report
      2010 Annual Research Report
  • [Book] マウス・ラット疾患モデル活用ハンドブック2011

    • Author(s)
      鈴木友子, 武田伸一
    • Total Pages
      605
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Book] Mechanosensing Biology2011

    • Author(s)
      Yuko Miyagoe-Suzuki, Shin'ichi Takeda
    • Total Pages
      219
    • Publisher
      Springer Japan
    • Related Report
      2010 Annual Research Report
  • [Book] Mechanosensing Biology(Mechanobiology in skeletal muscle : conversion of mechanical information into molecular signal.)(Springer Japan, ISBN 978-4-431-89756-9)2010

    • Author(s)
      鈴木友子, 武田伸一
    • Publisher
      ed.Masaki Noda
    • Related Report
      2010 Final Research Report
  • [Book] Muscle Cell Physiolog("Neuronal NOS as a regulator of muscle mass" : Editor : Yoshinobu Ohira.)(edited by Yoshinobu Ohira)2009

    • Author(s)
      Ito N, Miyagoe-Suzuki Y.
    • Publisher
      Osaka University Press
    • Related Report
      2010 Final Research Report
  • [Book] 炎症・再生医学事典(松島綱治・西脇徹編集「5.骨格筋」)2009

    • Author(s)
      鈴木友子,武田伸一
    • Publisher
      朝倉書店
    • Related Report
      2010 Final Research Report
  • [Book] Neuronal NOS as a regulator of muscle mass, Muscle Cell Physiology2009

    • Author(s)
      N.Ito, Y.Miyagoe-Suzuki
    • Total Pages
      11
    • Publisher
      Osaka University Press
    • Related Report
      2009 Annual Research Report
  • [Book] 炎症・再生医学事典「骨格筋」2009

    • Author(s)
      鈴木友子, 武田伸一
    • Total Pages
      4
    • Publisher
      朝倉書店
    • Related Report
      2009 Annual Research Report
  • [Book] Recent Advances of Skeletal muscle Differentiation(Side population (SP) cells and skeletal muscle differentiation.)(2008 : Editors : Kunihiro Tsuchida and Shin'ichi Takeda Research Signpost 378/661(2) Fort P.O., Trivandrum-695 023, Kerala, India)

    • Author(s)
      Miyagoe-Suzuki Y, Uezumi A, Takeda S
    • Related Report
      2010 Final Research Report
  • [Book] マウス・ラット疾患モデル活用ハンドブック(秋山徹・奥平隆平・河府和義編)(第23章:筋ジストロフィーモデルマウス)

    • Author(s)
      鈴木友子,武田伸一
    • Publisher
      羊土社
    • Related Report
      2010 Final Research Report
  • [Book] 第II部生物機能モデルの作製と利用(第3章糖鎖関連遺伝子ノックアウトマウス、第12節POMGnT1:「モデル動物利用マニュアル」)

    • Author(s)
      鈴木友子、遠藤玉夫
    • Publisher
      エル・アイ・シー
    • Related Report
      2010 Final Research Report
  • [Remarks] 研究部Home Page

    • URL

      http://www.ncnp.go.jp/nin/guide/r_dna2/index.html

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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