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Characterization of exosomes from HLA homozygous haplotype dental pulp cells and iPS cells

Research Project

Project/Area Number 17K11830
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionGifu University

Principal Investigator

Kawaguchi Tomoko  岐阜大学, 医学部附属病院, 医員 (30509815)

Co-Investigator(Kenkyū-buntansha) 飯田 一規  岐阜大学, 大学院医学系研究科, 講師 (30585237)
柴田 敏之  岐阜大学, 大学院医学系研究科, 教授 (50226172)
畠山 大二郎  岐阜大学, 医学部附属病院, 講師 (60377653)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords歯髄細胞 / エクソソーム / ハプロタイプホモ / 歯学 / 再生医学
Outline of Final Research Achievements

Human leukocyte antigens (HLA) play an important role in distinguishing self and non-self in the immune system. HLA multi-locus-homozygous cells are considered to be less likely to be rejected in allogeneic transplantation. In recent years, it has been reported that extracellular vesicles ~100 nm in diameter called exosomes are secreted from iPS cells and tissue stem cells, are partly responsible for cellular functions, and serve as a tool in intercellular communications such as those in immune reactions and tissue repair. In this study, we compared exosomes from HLA homozygous haplotype (HHH) dental pulp (DP) cells and exosomes from HHH-iPS cells derived from HHH-DP cells.
HHH-DP exosomes and HHH-iPS exosomes were found to have different expression profiles of miRNAs. HHH-iPS exosomes showed a reduced level of HLA expression. However, larger size-heterogeneity and less exosomal protein markers were also observed with HHH-iPS exosomes when compared with HHH-DP exosomes.

Academic Significance and Societal Importance of the Research Achievements

我々が3種類のHLAハプロタイプホモ歯髄細胞をすでに保管していることは、本研究を進めるうえでその意義は大きく、本研究により、HLAハプロタイプホモの歯髄細胞・iPS細胞の培養上清から、エクソソームを精製する技術の開発が可能となれば、エクソソームは内包する物質がもつ総合的な効果で細胞の性質を変化させる性質をもつ点で、既存の治療薬とは全く概念が異なり、再生医療の資源としてのDPCの価値は更に高くなると考えられる。また再生医療(臨床)に向けより安全な方法と考えられ、その意義は大きいと考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (13 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] FGF2-Responsive Genes in human Dental Pulp Cells Assessed using a Rat Spinal Cord Injury Model2018

    • Author(s)
      Ken Sugiyama, Kosuke Nagashima, Takahiro Miwa, Yuta Shimizu, Tomoko Kawaguchi, Kazuki Iida, Naritaka Tamaoki, Daijiro Hatakeyama, Hitomi Aoki, Chikara Abe, Hironobu Morita, Takahiro Kunisada, Toshiyuki Shibata, Hidefumi Fukumitsu, and Ken-ichi Tezuka
    • Journal Title

      Journal of Bone and Mineral Metabolism.

      Volume: 印刷中 Issue: 3 Pages: 467-474

    • DOI

      10.1007/s00774-018-0954-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Priming with FGF2 stimulates human dental pulp cells to promote axonal regeneration and locomotor function recovery after spinal cord injury2017

    • Author(s)
      Nagashima Kosuke、Miwa Takahiro、Soumiya Hitomi、Ushiro Daisuke、Takeda-Kawaguchi Tomoko、Tamaoki Naritaka、Ishiguro Saho、Sato Yumi、Miyamoto Kei、Ohno Takatoshi、Osawa Masatake、Kunisada Takahiro、Shibata Toshiyuki、Tezuka Ken-ichi、Furukawa Shoei、Fukumitsu Hidefumi
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 13500-13500

    • DOI

      10.1038/s41598-017-13373-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HLAハプロタイプホモiPS細胞からのエクソソーム精製2019

    • Author(s)
      清水雄太、川口知子、小足周平、柴田敏之、國貞隆弘、手塚健一
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Characterization and miRNA expression profiles of exosomes from HLA homozygous haplotype dental pulp cells and iPS cells2019

    • Author(s)
      Yuta Shimizu,Tomoko Kawaguchi,Shuhei Otari,Izumi Kuroda,Yuki Kuranaga,Hideya Kawasaki,Takahiko Hariyama,Toshiyuki Shibata,Takahiro Kunisada,Toshiaki Shibutani,Yukihiro Akao,Ken-ichi Tezuka
    • Organizer
      ANNUAL MEETING ISEV 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HLAハプロタイプホモ歯髄細胞およびiPS細胞由来エクソソームの特性化およびmiRNA発現比較2019

    • Author(s)
      清水雄太,川口知子,小足周平,澁谷俊昭
    • Organizer
      第150回春季日本歯科保存学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HLAハプロタイプホモ歯髄細胞由来エクソソームの特性評価および生物学的効果2019

    • Author(s)
      清水雄太、川口知子、小足周平、黒田依澄、堀田康明、柴田敏之、國貞隆弘、手塚建一
    • Organizer
      第62回秋季日本歯周病学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 歯髄細胞由来エクソソームによるLPS誘導性歯周炎の抑制効果2019

    • Author(s)
      清水雄太,川口知子,小足周平,黒田依澄,倉永祐希,堀田康明,河崎秀陽,針山孝彦,柴田敏之,赤尾幸博,國貞隆弘,手塚健一
    • Organizer
      第14回日本歯周病学会中部地区大学・日本臨床歯周病学会中部支部合同研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HLAハプロタイプホモiPS細胞からのエクソソーム精製2019

    • Author(s)
      清水雄太、川口知子、小足周平、柴田 敏之、國貞隆弘、手塚建一
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] HLAハプロタイプホモiPS細胞からのエクソソームの精製2018

    • Author(s)
      清水雄太、川口知子、小足周平、澁谷俊昭、手塚建一
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] HLA genome editing in human dental pulp stem cells using ZFN2018

    • Author(s)
      小足周平、青木仁美、川口知子、清水雄太、柴田敏之、國貞隆弘、澁谷俊昭、手塚建一
    • Organizer
      第104回アメリカ歯周病学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] HLA allele selective genome editing in human iPS cells using ZFN2018

    • Author(s)
      小足周平、青木仁美、川口知子、清水雄太、柴田敏之、國貞隆弘、手塚建一,澁谷俊昭
    • Organizer
      第66回国際歯科研究学会日本部会(JADR)学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] HLAハプロタイプホモiPS細胞からのエクソソームの精製2018

    • Author(s)
      清水雄太、川口知子、小足周平、黒田依澄、柴田 敏之、國貞隆弘、手塚建一、澁谷俊昭
    • Organizer
      第13回日本歯周病学会中部地区 大学・日本臨床歯周病学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒト歯髄細胞における脊髄損傷後の回復効果と相関するFGF2応答性遺伝子の検索2018

    • Author(s)
      杉山健、飯田一規、川口 知子、畠山大二郎、福光秀文、柴田敏之、国貞隆弘、手塚 建一
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒト歯髄細胞におけるHLAアリル選択的なゲノムエディティング2018

    • Author(s)
      小足周平、青木仁美、川口知子、清水雄太、柴田敏之、国貞隆弘、手塚 建一
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2017 Research-status Report
  • [Presentation] HLAはプロタイプホモiPS細胞からのエクソソームの精製2018

    • Author(s)
      清水雄太、川口知子、小足周平、澁谷俊昭、手塚建一
    • Organizer
      第36回日本骨代謝学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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