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The role of exosomes as a novel communication factor in tissue regeneration

Research Project

Project/Area Number 25253089
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionHiroshima University

Principal Investigator

OCHI MITSUO  広島大学, その他部局等, 学長 (70177244)

Co-Investigator(Kenkyū-buntansha) ADACHI NOBUO  広島大学, 大学院医歯薬保健学研究院, 教授 (30294383)
MIYAKI SHIGERU  広島大学, 病院, 講師 (10392490)
KAMEI NAOSUKE  広島大学, 病院, 講師 (70444685)
NAKASA TOMOYUKI  広島大学, 病院, 病院助教 (60467769)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000)
Fiscal Year 2015: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2014: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2013: ¥22,360,000 (Direct Cost: ¥17,200,000、Indirect Cost: ¥5,160,000)
Keywords組織再生 / 間葉系幹細胞 / エクソソーム / microRNA / miRNA
Outline of Final Research Achievements

Paracrine signaling by bone-marrow-derived mesenchymal stem cells (MSCs) plays a major role in tissue repair. We focused on exosomes, which are extracellular vesicles as a novel additional modulator of cell-to-cell communication and tissue regeneration. To address this, we examined the role of exosomes in the healing process in injury models of deficient mice, a strain which is known to reduce levels and/or function of exosomes. The retardation of tissue repair in deficient mice was rescued by the injection of MSC-exosomes. MSC-exosomes promoted cell differentiation such as myogenesis and angiogenesis in vitro, and tissue regeneration in tissue injury models. The levels of the tissue repair related-cytokines in MSC-exosomes were low, suggesting that, tissue repair may be in part mediated by other MSC-exosome components, such as miRNAs. We conclude that MSC-exosomes are a novel factor of MSC paracrine signaling with an important role in the tissue repair process.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (33 results)

All 2016 2015 2014 Other

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (26 results) (of which Invited: 18 results)

  • [Journal Article] Bach1 deficiency reduces severity of osteoarthritis through upregulation of heme oxygenase-12015

    • Author(s)
      Takada T, Miyaki S, Ishitobi H, Hirai Y, Nakasa T, Igarashi K, Lotz MK, Ochi M.
    • Journal Title

      Arthritis Res Ther

      Volume: 17 Issue: 1 Pages: 285-285

    • DOI

      10.1186/s13075-015-0792-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration.2015

    • Author(s)
      Nakamura Y, Miyaki S, Ishitobi H, Matsuyama S, Nakasa T, Kamei N, Akimoto T, Higashi Y, Ochi M.
    • Journal Title

      FEBS Lett

      Volume: 589 Issue: 11 Pages: 1257-65

    • DOI

      10.1016/j.febslet.2015.03.031

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] MicroRNAs and Bone Regeneration2015

    • Author(s)
      Nakasa T, Yoshizuka M, Andry Usman M, Elbadry Mahmoud E, Ochi M
    • Journal Title

      Curr Genomics

      Volume: 6 Issue: 6 Pages: 441-52

    • DOI

      10.2174/1389202916666150817213630

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stem cells in degenerative orthopaedic pathologies: effects of aging on therapeutic potential2015

    • Author(s)
      Atesok K, Fu FH, Sekiya I, Stolzing A, Ochi M, Rodeo SA.
    • Journal Title

      Knee Surg Sports Traumatol Arthrosc

      Volume: Epub ahead of print

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Combination therapy with intra-articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit2015

    • Author(s)
      Harada Y, Nakasa T, Mahmoud EE, Kamei G, Adachi N, Deie M, Ochi M.
    • Journal Title

      J Orthop Res

      Volume: 33 Issue: 10 Pages: 1466-73

    • DOI

      10.1002/jor.22922

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Exosomes from IL-1β stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes2014

    • Author(s)
      Kato T, Miyaki S, Ishitobi H, Nakamura Y, Nakasa T, Lotz MK, Ochi M.
    • Journal Title

      Arthritis Res Ther

      Volume: 4 August Issue: 4 Pages: 163-174

    • DOI

      10.1186/ar4679

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Exosome-formed synthetic microRNA-143 is transferred to osteosarcoma cells and inhibits their migration2014

    • Author(s)
      Shinbo K, Miyaki S, Ishitobi H, Kato Y, Kubo T, Shimose S, Ochi M
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 445 Issue: 2 Pages: 381-387

    • DOI

      10.1016/j.bbrc.2014.02.007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 間葉系幹細胞由来エクソソームは新たな組織再生因子である2016

    • Author(s)
      味八木茂、古田太輔、中邑祥博、石飛博之、越智光夫
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場(大阪市北区)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 変形性関節症におけるmicroRNAを含むエクソソーム2016

    • Author(s)
      味八木茂
    • Organizer
      第29回日本軟骨代謝学会
    • Place of Presentation
      広島大学広仁会館(広島市南区)
    • Year and Date
      2016-02-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] MSC由来エクソソームによるマウスモデルの骨折治癒の促進の検討2015

    • Author(s)
      古田太輔、味八木茂、石飛博之、越智光夫
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場(富山市大手町)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] MSC由来エクソソームによるマウスモデルの骨折治癒の促進の検討2015

    • Author(s)
      古田太輔、味八木茂、石飛博之、越智光夫
    • Organizer
      第33回日本骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-07-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mesenchymal stem cells-derived exosomes promote bone repair in mouse model2015

    • Author(s)
      Furuta T, Miyaki S, Ishitobi H, Kamei N, Miyado K, Ochi M
    • Organizer
      Orthopaedic Research Society 2015 Annual Meeting
    • Place of Presentation
      Las Vegas, U.S.A
    • Year and Date
      2015-03-28 – 2015-03-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] テトラスパニンCD9,エクソソームと骨折治癒の検討2014

    • Author(s)
      古田大輔、味八木茂、石飛博之、住吉範彦、越智光夫
    • Organizer
      第29回日本整形外科学会基礎学術集会
    • Place of Presentation
      城山観光ホテル(鹿児島市新照院町)
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] microRNAを含む間葉系幹細胞由来エクソソームは骨格筋再生を促進する2014

    • Author(s)
      中邑祥博、味八木茂、石飛博之、中佐智幸、亀井直輔、越智光夫
    • Organizer
      第29回日本整形外科学会基礎学術集会
    • Place of Presentation
      城山観光ホテル(鹿児島市新照院町)
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] THE ROLE OF TETRASPANIN CD9 IN PATHOGENESIS OF OSTEOARTHRITIS2014

    • Author(s)
      Sumiyoshi N, Miyaki S, Takada T, Ishitobi H, Nakasa T, Ochi, M
    • Organizer
      Osteoarthritis Research Society International world congress
    • Place of Presentation
      Paris, France
    • Year and Date
      2014-04-24 – 2014-04-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Exosomes derived from mesenchymal stem cells accelerate skeletal muscle regeneration.2014

    • Author(s)
      Y. Nakamura, H. Ishitobi, T. Kato, T. Takada, T. Nakasa, M. Lotz, S. Miyaki, M. Ochi
    • Organizer
      Orthopaedic Research Society 2014
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mesenchymal stem cell-derived exosomes containing microRNAs accelerate skeletal muscle regeneration.2014

    • Author(s)
      Yoshihiro Nakamura, Shigeru Miyaki, Hiroyuki Ishitobi, Tomoyuki Nakasa, Naosuke Kamei, Mitsuo Ochi
    • Organizer
      International Society for Extracellular Vesicles 2014
    • Place of Presentation
      Rotterdam, Nederland
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 我が国における軟骨再生治療の現状と展望

    • Author(s)
      越智光夫
    • Organizer
      第1回軟骨再生医療レギュラトリーサイエンスフォーラム
    • Place of Presentation
      東京女子医科大学先端生命医科学研究所(東京都新宿区)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 軟骨の再生医療 -基礎から臨床への道-

    • Author(s)
      越智光夫
    • Organizer
      第120回中部日本整形外科災害外科学会・学術集会
    • Place of Presentation
      和歌山県民文化会館他(和歌山市小松原通り)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Cartilage Repair Options: Do we need cells to restore chondral surfaces?

    • Author(s)
      Mitsuo Ochi
    • Organizer
      9th BIENNIAL ISAKOS CONGRESS.
    • Place of Presentation
      Tronto, Canada.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Cartilage repair. -past, present and future-.

    • Author(s)
      Mitsuo Ochi
    • Organizer
      15th Annual Meeting of Korean Tissue Engineering and Regenerative Medicine Society.
    • Place of Presentation
      Seoul, Korea.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 関節軟骨再生へのチャレンジ 変形性膝関節症を含む

    • Author(s)
      越智光夫
    • Organizer
      第67回日本交通医学会総会
    • Place of Presentation
      ホテルグランヴィア広島(広島市南区)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 関節軟骨再生 -過去、現在、未来-

    • Author(s)
      越智光夫
    • Organizer
      第34回日本炎症・再生医学会
    • Place of Presentation
      国立京都国際会館(京都市左京区)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Cartilage repair -past, present and future-.

    • Author(s)
      Mitsuo Ochi
    • Organizer
      University of Pennsylvania, Visiting Professor lecture.
    • Place of Presentation
      Philadelphia. USA.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Cartilage repair -past, present and future-.

    • Author(s)
      Mitsuo Ochi
    • Organizer
      Department of Orthopaedic Surgery -Grand Rounds, Visiting Professor lecture.
    • Place of Presentation
      University of California, Irvine. USA.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] What is the Future of Cartilage Repair? Cartilage Repair by Cell Therapy.

    • Author(s)
      Mitsuo Ochi
    • Organizer
      International Symposium on Cartilage Repair of the Ankle Asia.
    • Place of Presentation
      Roppongi Academyhills , Tokyo, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Future Treatments for Cartilage Defects.

    • Author(s)
      Mitsuo Ochi
    • Organizer
      The 1st Annual Meeting of Indonesian Orthopedic Society for Sports Medicine & Arthroscopy (IOSSMA).
    • Place of Presentation
      Jakarta, Indonesia.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Cartilage repair -past, present, future.

    • Author(s)
      Mitsuo Ochi
    • Organizer
      12th National Congress of the Bulgarian Orthopaedic and Traumatologic Association with International Participation.
    • Place of Presentation
      Varna, Bulgaria.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 運動器の再生医療 -軟骨、骨、筋、靭帯、末梢神経-

    • Author(s)
      越智光夫
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      幕張メッセ国際会議場(千葉市美浜区)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 関節軟骨変性・再生

    • Author(s)
      越智光夫
    • Organizer
      第41回日本関節病学会
    • Place of Presentation
      愛知県産業労働センター ウインクあいち(名古屋市中村区)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Cutting - Edge Technology for Cartilage Repair.

    • Author(s)
      Mitsuo Ochi
    • Organizer
      Combined Congress of Asian Cartilage Repair Society and Indian Cartilage Society.
    • Place of Presentation
      Chennai, India.
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] New Horizon for cartilage repair.

    • Author(s)
      Mitsuo Ochi
    • Organizer
      Sweden Embassy Medical Forum
    • Place of Presentation
      Sweden Embassy, Tokyo, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 間葉系幹細胞由来のエクソソームは骨格筋再生を促進する

    • Author(s)
      味八木茂、中邑祥博、石飛博之、中佐智幸、亀井直輔、越智光夫
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      国立京都国際会館(京都市左京区)
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-05-15   Modified: 2019-07-29  

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