Study on molecular regulation of muscle regeneration by mesenchymal cells

• Project/Area Number: 20590418
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: National 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: ¥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.

Research Products

• [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 13(2) Pages: 170-82
  • Peer Reviewed
• [Journal Article] Reactive gliosis of astrocytes and Muller glial cells in retina of POMGnT1-deficient mice (2011)
  • 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
  • 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
  • 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. 176(5) Pages: 2414-24
  • Peer Reviewed
• [Journal Article] Gene therapy for muscle disease. Mini-review (2010)
  • Author(s): Miyagoe-Suzuki Y, Takeda S
  • Journal Title: Exp.Cell Res.(Epub 2010 May 24. Review) 316(18) Pages: 3087-92
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
  • Peer Reviewed
• [Journal Article] Genetic Background Affects Properties of Satellite Cells and mdx Phenotypes (2010)
  • 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)
  • 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
  • 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
  • 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
  • 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 S, Yamamoto H, Motohashi N, Miyagoe-Suzuki Y, Takeda S, Heike T, Nakahata T
  • Journal Title: FASEB J. 23 Pages: 1907-1919
  • 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
• [Journal Article] Reduced proliferative activity of primary POMGnT1-null myoblasts in vitro (2009)
  • Author(s): Miyagoe-Suzuki Y, et al.
  • Journal Title: Mechanisms of Development 126 Pages: 107-116
  • 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, et al.
  • Journal Title: Human Molecular Genetics 18 Pages: 621-631
  • Peer Reviewed
• [Journal Article] Generation of transplantable, functional satellite-like cells from mouse embryonic stem cells (2009)
  • Author(s): Chang H, et al.
  • Journal Title: The FASEB Journal (印刷中)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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, et al.
  • Journal Title: Human Gene Therapy 19 Pages: 719-730
  • Peer Reviewed
• [Journal Article] Downstream utrophin enhancer is required for expression of utrophin in skeletal muscle (2008)
  • Author(s): Tanihata J, et al.
  • Journal Title: Journal of Gene Medicine 10 Pages: 702-713
  • 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, et al.
  • Journal Title: American Journal of Pathology 173 Pages: 781-791
  • Peer Reviewed
• [Journal Article] Suppression of macrophage functions impairs skeletal muscle regeneration with severe fibrosis (2008)
  • Author(s): Segawa M, et al.
  • Journal Title: Experimental Cell Research 314 Pages: 3232-3244
  • 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
  • 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
• [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
• [Presentation] nNOS regulates skeletal muscle mass (2009)
  • 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
• [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
• [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
• [Presentation] Making muscle from induced pluripotent stem(iPS)cells (2009)
  • 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
• [Presentation] Making muscle from induced pluripotent stem (iPS) cells. Institute de Myologie, Hopital de la Salpetriere, Paris (2009)
  • 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-
• [Presentation] Abnormal glycosylation of alpha-dystroglycan results in poor proliferation and limited migration of muscle satellite cells (2008)
  • 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
• [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
• [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
• [Book] Mechanosensing Biology (2011)
  • Author(s): Yuko Miyagoe-Suzuki, Shin'ichi Takeda
  • Total Pages: 219
  • Publisher: Springer Japan
• [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
• [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
• [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
• [Book] Neuronal NOS as a regulator of muscle mass, Muscle Cell Physiology (2009)
  • Author(s): N.Ito, Y.Miyagoe-Suzuki
  • Total Pages: 11
  • Publisher: Osaka University Press
• [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
• [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
• [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
• [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
• [Remarks] 研究部Home Page
  • URL: http://www.ncnp.go.jp/nin/guide/r_dna2/index.html