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Elucidation of bone regenerative mechanism after mesenchymal stem cell spheroid transplantation

Research Project

Project/Area Number 20K23012
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0906:Surgery related to the biological and sensory functions and related fields
Research InstitutionKindai University

Principal Investigator

Mizukami Yuya  近畿大学, 医学部, 助教 (20881163)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords骨再生 / 間葉系幹細胞 / スフェロイド / 細胞スフェロイド
Outline of Research at the Start

間葉系幹細胞(MSC)の骨再生治療への応用が期待されている。近年、MSCをスフェロイドにすることで高い骨修復・再生に対する効果を誘導できることが示唆されている。しかし、スフェロイド化により生じるMSCの分化シグナルの変化やMSCの分泌因子を介した周辺細胞への影響は不明であり、MSCスフェロイドが骨再生に有効なメカニズムは不明である。本研究では、MSCスフェロイドの分化シグナルおよび、細胞分化による周辺細胞への影響を解析することで、MSCの移植治療における新たな骨再生メカニズムを明らかにすることを目指す。

Outline of Final Research Achievements

In this study, I challenged to elucidate the bone regeneration mechanism of mesenchymal stem cell spheroids, which have been reported to show high bone regeneration capacity. Adipose tissue-derived mesenchymal stem cells (ADSCs) spheroids were fabricated and transplanted into femoral bone defects of healthy mice and streptozotocin-induced diabetic model mice. However, ADSCs spheroids showed no significant bone regeneration effect. In addition, the bone regeneration effect of ADSCs spheroids was not improved by changing the scaffold material, the number of transplanted cells, or the spheroid size. Therefore, ADSCs spheroids did not show the expected bone regeneration effect, and so the mechanism of bone regeneration promotion of ADSCs spheroids could not be elucidated.

Academic Significance and Societal Importance of the Research Achievements

健康寿命の延伸を目的とした、加齢や糖尿病、ステロイド治療により骨が脆弱化した患者の骨折治癒や骨再生治療法の開発が求められている。間葉系幹細胞は骨再生を促進することから、間葉系幹細胞移植の骨再生治療への応用研究がこれまでにも進められてきた。近年、スフェロイド化した間葉系幹細胞の移植が効率的な骨再生を誘導することが報告され、臨床への応用が期待されている。しかし本研究では、脂肪組織由来の間葉系幹細胞スフェロイドは、骨再生に対して有意な促進効果を示さなかった。本研究は間葉系幹細胞スフェロイド移植による効果的な骨再生治療法の確立に対して、移植細胞、移植方法に関する新たな課題を提示した。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2022 2021

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 5 results)

  • [Journal Article] Role of peripheral myelin protein 22 in chronic exercise‐induced interactions of muscle and bone in mice2022

    • Author(s)
      Kawaguchi Miku、Kawao Naoyuki、Muratani Masafumi、Takafuji Yoshimasa、Ishida Masayoshi、Kinoshita Yuko、Takada Yuto、Mizukami Yuya、Ohira Takashi、Kaji Hiroshi
    • Journal Title

      Journal of Cellular Physiology

      Volume: - Issue: 5 Pages: 1-11

    • DOI

      10.1002/jcp.30706

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Renal failure suppresses muscle irisin expression, and irisin blunts cortical bone loss in mice2022

    • Author(s)
      Kawao Naoyuki、Kawaguchi Miku、Ohira Takashi、Ehara Hiroki、Mizukami Yuya、Takafuji Yoshimasa、Kaji Hiroshi
    • Journal Title

      Journal of Cachexia, Sarcopenia and Muscle

      Volume: 13 Issue: 1 Pages: 758-771

    • DOI

      10.1002/jcsm.12892

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calcium Peroxide-Containing Polydimethylsiloxane-Based Microwells for Inhibiting Cell Death in Spheroids through Improved Oxygen Supply2021

    • Author(s)
      Mizukami Yuya、Takahashi Yuki、Shimizu Kazunori、Konishi Satoshi、Takakura Yoshinobu、Nishikawa Makiya
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 44 Issue: 10 Pages: 1458-1464

    • DOI

      10.1248/bpb.b21-00269

    • NAID

      130008095763

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2021-10-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of plasminogen activator inhibitor-1 in muscle wasting induced by a diabetic state in female mice2021

    • Author(s)
      Ehara Hiroki、Takafuji Yoshimasa、Tatsumi Kohei、Okada Kiyotaka、Mizukami Yuya、Kawao Naoyuki、Matsuo Osamu、Kaji Hiroshi
    • Journal Title

      Endocrine Journal

      Volume: 68 Issue: 12 Pages: 1421-1428

    • DOI

      10.1507/endocrj.EJ21-0142

    • NAID

      130008136479

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serpinb1a suppresses osteoclast formation2021

    • Author(s)
      Ishida Masayoshi、Kawao Naoyuki、Mizukami Yuya、Takafuji Yoshimasa、Kaji Hiroshi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 26 Pages: 101004-101004

    • DOI

      10.1016/j.bbrep.2021.101004

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of Angptl1 on osteoclast formation and osteoblastic phenotype in mouse cells2021

    • Author(s)
      Ishida Masayoshi、Kawao Naoyuki、Mizukami Yuya、Takafuji Yoshimasa、Kaji Hiroshi
    • Journal Title

      BMC Musculoskeletal Disorders

      Volume: 22 Issue: 1 Pages: 398-398

    • DOI

      10.1186/s12891-021-04278-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Micro RNA 196a-5p in extracellular vesicles secreted from myoblasts suppresses osteoclast-like cell formation in mouse cells.2021

    • Author(s)
      Takafuji Y, Tatsumi K, Kawao N, Okada K, Muratani M, Kaji H.
    • Journal Title

      Calcif Tissue 108(3):364-376

      Volume: 108 Issue: 4 Pages: 364-376

    • DOI

      10.1007/s00774-020-01201-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed

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Published: 2020-09-29   Modified: 2023-01-30  

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