筋衛星細胞の質と量を制御する機構の解明とその制御

• Project Area: Establishing a new paradigm of the pathogenesis of diseases through the understanding of stem cell aging
• Project/Area Number: 15H01521
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Keio University
• Principal Investigator: 湯浅 慎介 慶應義塾大学, 医学部(信濃町), 講師 (90398628)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: 骨格筋 / 幹細胞 / 再生 / サイトカイン

Outline of Annual Research Achievements

骨格筋の幹細胞である筋衛星細胞は、通常は静止期にあるが筋傷害に反応し活性化・増殖・分化し、筋芽細胞を経て融合し成熟骨格筋細胞となり、筋肉としての機能維持を担っている。本研究においては『筋衛星細胞の質と量を制御する機構を解明し、筋肉におけるステムセルエイジングの制御』を目的とする。骨格筋ステムセルエイジングに伴い骨格筋の再生能の低下や再生骨格筋の機能低下が想定され、骨格筋ステムセルエイジング正しく理解し制御する方法を開発することは、あらゆる骨格筋疾患の治療に繋がり意義のあることである。早期に骨格筋ステムセルエイジングを来すモデルとして、マウス筋ジストロフィーモデルを用いた解析を行った。筋ジストロフィーは慢性の骨格筋傷害の結果、骨格筋再生が常に促されており、早期にステムセルエイジングを来す。筋ジストロフィーモデルにおいて、骨格筋の幹細胞である筋衛星細胞の詳細な解析を行い、筋衛星細胞の老化に伴うステムセルエイジングとG-CSFとの関わりをin vivoにおいて解析し、G-CSFがステムセルエイジングを制御できることを見出した。また筋ジストロフィー治療方法開発へ向けた、G-CSF投与の至適な量や時期等を検討した。さらに加齢に伴いゆるやかにステムセルエイジングに至ることが想定されるが、加齢に伴う筋衛星細胞の老化、骨格筋再生能低下によるサルコペニアにおける筋衛星細胞の数と機能改善へ向けた研究を行った。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Patient confidence regarding secondary lifestyle modification and knowledge of 'heart attack' symptoms following percutaneous revascularisation in Japan: a cross-sectional study. (2018)
  • Author(s): Kitakata H, Kohno T, Kohsaka S, Fujino J, Nakano N, Fukuoka R, Yuasa S, Maekawa Y, Fukuda K.
  • Journal Title: BMJ Open. Volume: 8(3)
  • DOI: 10.1136/bmjopen-2017-019119
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous Occlusion of Patent Ductus Arteriosus for an Elderly Patient With Refractory Congestive Heart Failure. (2018)
  • Author(s): Shoji S, Kanazawa H, Yanagisawa R, Tanaka M, Fukuoka R, Akita K, Kimura M, Arai T, Kawakami T, Hayashida K, Yuasa S, Tsuruta H, Itabashi Y, Murata M, Nishiyama T, Kohno T, Maekawa Y, Fukuda K.
  • Journal Title: Circ Heart Fail. Volume: 2
  • DOI: 10.1161/circheartfailure.117.004764
  • Peer Reviewed
• [Journal Article] Characteristics and in-hospital outcomes in young patients presenting with acute coronary syndrome treated by percutaneous coronary intervention. (2018)
  • Author(s): Hirota Y, Sawano M, Numasawa Y, Ueda I, Noma S, Suzuki M, Hayashida K, Yuasa S, Maekawa Y, Kohsaka S, Fukuda K.
  • Journal Title: Cardiovasc Interv Ther. Volume: 33(2) Pages: 154-162
  • DOI: 10.1007/s12928-017-0471-z
  • Peer Reviewed
• [Journal Article] Predictors of high cost after percutaneous coronary intervention: A review from Japanese multicenter registry overviewing the influence of procedural complications. (2017)
  • Author(s): Inohara T, Numasawa Y, Higashi T, Ueda I, Suzuki M, Hayashida K, Yuasa S, Maekawa Y, Fukuda K, Kohsaka S.
  • Journal Title: Am Heart J. Volume: 194 Pages: 61-72
  • DOI: 10.1016/j.ahj.2017.08.008
  • Peer Reviewed
• [Journal Article] Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes (2017)
  • Author(s): Kuroda Y, Yuasa S, Watanabe Y, Ito S, Egashira T, ・・・Horie M, Kamiya K, Fukuda K.
  • Journal Title: Biochemistry and biophysics reports Volume: 9 Pages: 245-256
  • DOI: 10.1016/j.bbrep.2017.01.002
  • Peer Reviewed / Open Access
• [Journal Article] Epigenetic barrier against the propagation of fluctuating gene expression in embryonic stem cells. (2017)
  • Author(s): Saito Y, Kunitomi A, Seki T, Tohyama S, Kusumoto D, Takei M, Kashimura S, Hashimoto H, Yozu G, Motoda C, Shimojima M, Egashira T, Oda M, Fukuda K, Yuasa S.
  • Journal Title: FEBS Lett. Volume: 591(18) Pages: 2879-2889
  • DOI: 10.1002/1873-3468.12791
  • Peer Reviewed
• [Journal Article] Barriers Associated With Door-to-Balloon Delay in Contemporary Japanese Practice (2017)
  • Author(s): Ikemura N, Sawano M, Shiraishi Y, Ueda I, Miyata H, Numasawa Y, Noma S, Suzuki M, Momiyama Y, Inohara T, Hayashida K, Yuasa S, Maekawa Y, Fukuda K, Kohsaka S.
  • Journal Title: Circ J. Volume: Epub ahead of print Issue: 6 Pages: 815-822
  • DOI: 10.1253/circj.CJ-16-0905
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient (2017)
  • Author(s): Shimojima M, Yuasa S, Motoda C, Yozu G, Nagai T, Ito S, Lachmann M, Kashimura S, Takei M, Kusumoto D, Kunitomi A, Hayashiji N, Seki T, Tohyama S, Hashimoto H, Kodaira M, Egashira T, Hayashi K, Nakanishi C, Sakata K, Yamagishi M, Fukuda K.
  • Journal Title: Sci Rep. Volume: 7 Pages: 44312-44312
  • DOI: 10.1038/srep44312
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nocturnal intermittent hypoxia and short sleep duration are independently associated with elevated C-reactive protein levels in patients with coronary artery disease. (2017)
  • Author(s): Fukuoka R, Kohno T, Kohsaka S, Yanagisawa R, Kawakami T, Hayashida K, Kanazawa H, Yuasa S, Maekawa Y, Sano M, Fukuda K.
  • Journal Title: Sleep Med. Volume: 29 Pages: 29-34
  • DOI: 10.1016/j.sleep.2016.09.012
  • Peer Reviewed
• [Journal Article] An RyR2 mutation found in a family with a short-coupled variant of torsade de pointes. (2017)
  • Author(s): Kimura M, Fujisawa T, Aizawa Y, Matsuhashi N, Ito S, Nakajima K, Kashimura S, Kunitomi A, Katsumata Y, Nishiyama T, Kimura T, Nishiyama N, Yuasa S, Takatsuki S, Kosaki K, Fukuda K.
  • Journal Title: Int J Cardiol. Volume: 227 Pages: 367-369
  • Peer Reviewed
• [Journal Article] Embryonic type Na+ channel beta-subunit, SCN3B masks the disease phenotype of Brugada syndrome (2016)
  • Author(s): Kushiyama Y, Honjo H, Niwa R, Takanari H, Yamazaki M, Takemoto Y, Sakuma I, Kodama I, Kamiya K
  • Journal Title: Scientific Reports Volume: 311 Pages: 34198-34198
  • DOI: 10.1038/srep34198
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Glutamine Oxidation is Indispensable for Survival of Human Pluripotent Stem Cells. (2016)
  • Author(s): Tohyama S, Fujita J, Hishiki T, Matsuura T, Hattori F, Ohno R, Kanazawa H, Seki T, Nakajima K, Kishino Y, Okada M, Hirano A, Kuroda T, Yasuda S, Sato Y, Yuasa S, Sano M, Suematsu M, Fukuda K.
  • Journal Title: Cell Metab. Volume: 23 Pages: 663-674
  • DOI: 10.1016/j.cmet.2016.03.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A Novel Wire-Assisted Technique for Closing Large Atrial Septal Defects: New Concepts of Closure Mechanism. (2016)
  • Author(s): Kanazawa H, Kawamura A, Kimura M, Akita K, Yashima F, Arai T, Kawakami T, Hayashida K, Tsuruta H, Yuasa S, Itabashi Y, Murata M, Maekawa Y, Fukuda K.
  • Journal Title: JACC Cardiovasc Interv Volume: 9
  • DOI: 10.1016/j.jcin.2015.12.016
  • Peer Reviewed
• [Journal Article] In-Stent Dissection Causes No Flow During Percutaneous Coronary Intervention. (2016)
  • Author(s): Yashima F, Yuasa S, Maekawa Y, Kimura M, Akita K, Yanagisawa R, Tanaka M, Hayashida K, Kawakami T, Kanazawa H, Fujita J, Fukuda K.
  • Journal Title: JACC Cardiovasc Interv. Volume: 9 Pages: 9-9
  • DOI: 10.1016/j.jcin.2015.09.025
  • Peer Reviewed
• [Journal Article] "Moving left ventricular obstruction" due to stress cardiomyopathy in a patient with hypertrophic obstructive cardiomyopathy treated with percutaneous transluminal septal myocardial ablation. (2016)
  • Author(s): Akita K, Maekawa Y, Tsuruta H, Okuda S, Yanagisawa R, Kageyama T, Kawakami T, Kanazawa H, Hayashida K, Yuasa S, Murata M, Jinzaki M, Fukuda K.
  • Journal Title: Int J Cardiol Volume: 202 Pages: 194-195
  • DOI: 10.1016/j.ijcard.2015.08.145
  • Peer Reviewed
• [Journal Article] Patient-Specific Induced Pluripotent Stem Cell Models: Characterization of iPS Cell-Derived Cardiomyocytes. (2016)
  • Author(s): Egashira T, Yuasa S, Tohyama S, Kuroda Y, Suzuki T, Seki T, Fukuda K.
  • Journal Title: Methods Mol Biol. 2016;1353:343-53. Volume: 1353 Pages: 343-353
  • DOI: 10.1007/7651_2014_165
  • Peer Reviewed
• [Journal Article] Generation of Induced Pluripotent Stem Cells from Human Peripheral T Cells Using Sendai Virus in Feeder-free Conditions. (2015)
  • Author(s): Kishino Y, Seki T, Yuasa S, Fujita J, Fukuda K.
  • Journal Title: J Vis Exp Volume: 105 Pages: 105-105
  • DOI: 10.3791/53225
  • Peer Reviewed
• [Journal Article] "Protruding Myocardium" as a Target for Percutaneous Transluminal Septal Myocardial Ablation in a Case of Hypertrophic Obstructive Cardiomyopathy. (2015)
  • Author(s): Maekawa Y, Akita K, Tsuruta H, Yashima F, Kimura M, Yamada Y, Kawakami T, Kanazawa H, Hayashida K, Yuasa S, Murata M, Jinzaki M, Fukuda K.
  • Journal Title: JACC Cardiovasc Interv. Volume: 8 Pages: 201-202
  • DOI: 10.1016/j.jcin.2015.05.029
  • Peer Reviewed
• [Journal Article] Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells. (2015)
  • Author(s): Tanaka A, Yuasa S, Node K, Fukuda K.
  • Journal Title: Int J Mol Sci. Volume: 16 Pages: 18894-922
  • DOI: 10.3390/ijms160818894
  • Peer Reviewed
• [Journal Article] Analysis of cardiomyocyte movement in the developing murine heart. (2015)
  • Author(s): Hashimoto H, Yuasa S, Tabata H, Tohyama S, Seki T, Egashira T, Hayashiji N, Hattori F, Kusumoto D, Kunitomi A, Takei M, Kashimura S, Yozu G, Shimojima M, Motoda C, Muraoka N, Nakajima K, Sakaue-Sawano A, Miyawaki A, Fukuda K
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 464 Pages: 1000-1007
  • DOI: 10.1016/j.bbrc.2015.07.036
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The Role of Circadian Rhythms in Fatal Arrhythmias and the Potential Impact of Intervention for Sleep-Disordered Breathing. (2015)
  • Author(s): Aizawa Y, Kohno T, Yuasa S, Fukuda K.
  • Journal Title: Curr Pharm Des. Volume: 21 Pages: 3512-22
  • Peer Reviewed
• [Journal Article] G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy. (2015)
  • Author(s): Hayashiji N, Yuasa S, Miyagoe-Suzuki Y, Hara M, Ito N, Hashimoto H, Kusumoto D, Seki T, Tohyama S, Kodaira M, Kunitomi A, Kashimura S, Takei M, Saito Y, Okata S, Egashira T, Endo J, Sasaoka T, Takeda S, Fukuda K
  • Journal Title: Nat Commun. Volume: 6 Pages: 6745-6745
  • DOI: 10.1038/ncomms7745
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lesion morphological classification by OCT to predict therapeutic efficacy after balloon pulmonary angioplasty in CTEPH. (2015)
  • Author(s): Inohara T, Kawakami T, Kataoka M, Yamamoto M, Kimura M, Kanazawa H, Yuasa S, Hayashida K, Maekawa Y, Fukuda K.
  • Journal Title: Lesion morphological classification by OCT to predict therapeutic efficacy after balloon pulmonary angioplasty in CTEPH. Volume: 197 Pages: 2015-2015
  • DOI: 10.1016/j.ijcard.2015.06.036
  • Peer Reviewed
• [Presentation] Arrhythmogenic disease modeling using iPS cells (2018)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 1st JCS Council Forum on Basic CardioVascular Research
  • Int'l Joint Research / Invited
• [Presentation] iPS細胞を用いた心不全の診断 (2017)
  • Author(s): 湯浅慎介
  • Organizer: 日本心不全学会
  • Invited
• [Presentation] Cardiac Arrhythmia Modeling by Induced Pluripotent Stem Cells (2017)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session In Conjunction with the Annual Meeting of the Japanese Heart Rhythm Society
  • Int'l Joint Research / Invited
• [Presentation] Disease modeling by iPS cells (2017)
  • Author(s): Shinsuke Yuasa
  • Organizer: The 10th Asia Pacific Heart Rhythm Society Scientific Session In Conjunction with the Annual Meeting of the Japanese Heart Rhythm Society
  • Int'l Joint Research / Invited
• [Presentation] iPS細胞を用いた循環器疾患の病態解明 (2017)
  • Author(s): 湯浅慎介
  • Organizer: 日本炎症・再生医学会
  • Invited
• [Presentation] iPS細胞を用いた心筋症の病態解明 (2017)
  • Author(s): 湯浅慎介
  • Organizer: 第3回 日本心筋症研究会
  • Invited
• [Presentation] Arrhythmogenic Disease Modeling by iPS Cells. (2017)
  • Author(s): 湯浅慎介
  • Organizer: The 81st Annual Scientific Meeting of the Japanese Circulation Society.
  • Invited
• [Presentation] iPS細胞を用いた肥大型心筋症の治療方法の開発 (2016)
  • Author(s): 湯浅慎介
  • Organizer: 第20回日本心不全学会
  • Invited
• [Presentation] G-CSFによる骨格筋幹細胞維持機構と筋疾患治療への応用 (2016)
  • Author(s): 湯浅慎介
  • Organizer: 第89回日本生化学会大会
  • Invited
• [Presentation] iPS細胞を用いた循環器疾患の解析 (2016)
  • Author(s): 湯浅慎介
  • Organizer: 第37回日本炎症・再生医学会
  • Invited