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Analysis of the mechanism of wound healing and anti-inflammatory action by mesenchymal stem cell exosomes

Research Project

Project/Area Number 23K24531
Project/Area Number (Other) 22H03273 (2022-2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2022-2023)
Section一般
Review Section Basic Section 57040:Regenerative dentistry and dental engineering-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

岩田 隆紀  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (60431946)

Co-Investigator(Kenkyū-buntansha) 丸川 恵理子  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (40419263)
朴 聖俊  東京大学, 医科学研究所, 准教授 (40759411)
水谷 幸嗣  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (60451910)
Project Period (FY) 2022-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2025: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2024: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2023: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2022: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywordsエクソソーム / 再生医療 / 間葉系幹細胞 / miRNA / 創傷治癒 / 創傷治癒作用 / 抗炎症作用
Outline of Research at the Start

間葉系幹細胞が分泌するエクソソームを精製し、特に創傷治癒効果と抗炎症作用に着目しながらエクソソーム中の重要特性因子を同定する。特にmicroRNAとタンパクを中心に解析を進める。さらには様々な種類や状態の細胞からエクソソームを抽出し、網羅的なプロファイリングすることで、疾患に合わせたエクソソームの選択技術を確立する。

Outline of Annual Research Achievements

今年度においては、昨年度確立したエクソソームの単離方法を基に、その保存方法の最適化を追加で行った。そして先行研究にて骨誘導能が比較的高いことが判明しているヒト歯根膜幹細胞株(P034)から得られたエクソソームを精製し、ヒト歯根膜幹細胞に対する効果を検証したところ、抗炎症能は見られなかったが、顕著な骨誘導能と創傷治癒能の促進は確認できた。
エクソソーム内で上記効能を有しているmiRNAを見出すため、昨年度より計画していたマイクロアレイを用い、P304と骨誘導能が低いヒト歯根膜幹細胞株(P309)のエクソソーム内miRNAを比較しプロファイリングを行ったところ、20の候補miRNAを特定した。文献報告に基づき、さらに8つへ絞り込んだ後、mimicを用いた過剰発現と阻害剤を用いた発現抑制でそれらの検証を行った際には、エクソソームの直接添加と類似した表現型を有するmiRNAの特定に成功した。
また、特定したmiRNAのターゲットmRNAを見つけるため、既存のデータベース(miRbase等)による予測を試みたが、依然候補が多くルシフェラーゼアッセイなどでは手間がかかるため、RIP-Seq(RNA immunoprecipitation sequence)による確認を考案した。この手法により、mimicによる過剰発現を行った後、miRNAとmRNAが結合状態にあるRISC(RNA-induced silencing complex)を免疫沈降することで、結合しているmRNAを回収し、予測ではなく、直接的にmiRNAの結合対象を見つけることが可能になる。2023年度末の時点において、その条件検討の最適化が完了した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

今年度でエクソソームの骨誘導能と創傷治癒能を確認できた上に、寄与しているmiRNAも特定できたので、昨年度の客観的条件による遅れを取り戻せたと言える。

Strategy for Future Research Activity

エクソソームの効用の確認と、寄与しているmiRNAの特定は完了しており、miRNAの作用対象を特定する方法も最適化済みである。次年度は作用対象であるmRNAを特定した後、初歩的にヒト歯根膜細胞由来のエクソソームが歯周組織再生に寄与するメカニズムを明確にし、その結果に連なる創薬関連の特許申請も視野に入れている。また、miRNAの絞り込み過程で異なる効能を有するmiRNAも発見したため、余裕がある場合は、それらの関連性や、選択的にエクソソームへローディングされる上流的なメカニズムも検討する予定である。

Report

(2 results)
  • 2023 Annual Research Report
  • 2022 Annual Research Report
  • Research Products

    (26 results)

All 2023 2022

All Journal Article (26 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 24 results,  Open Access: 20 results)

  • [Journal Article] Association between periodontal disease and chronic obstructive pulmonary disease2023

    • Author(s)
      Lin P, Liu A, Tsuchiya Y, Noritake K, Ohsugi Y, Toyoshima K, Tsukahara Y, Shiba T, Nitta H, Aoki A, Iwata T, Katagiri S.
    • Journal Title

      Japanese Dental Science Review

      Volume: 59 Pages: 389-402

    • DOI

      10.1016/j.jdsr.2023.10.004

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of Different Wavelengths of LED Lights in Antimicrobial Photodynamic Therapy for the Treatment of Periodontal Disease2023

    • Author(s)
      Takeuchi Yasuo、Aoki Akira、Hiratsuka Koichi、Chui Chanthoeun、Ichinose Akiko、Aung Nay、Kitanaka Yutaro、Hayashi Sakura、Toyoshima Keita、Iwata Takanori、Arakawa Shinich
    • Journal Title

      Antibiotics

      Volume: 12 Issue: 12 Pages: 1676-1676

    • DOI

      10.3390/antibiotics12121676

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of low‐level Er:YAG laser irradiation on proliferation and gene expression in primary gingival fibroblasts isolated from mouse maxilla2023

    • Author(s)
      Lin P, Niimi H, Hirota T, Ohsugi Y, Shimohira T, Toyoshima K, Katagiri S, Iwata T, Aoki A.
    • Journal Title

      Journal of Biophotonics

      Volume: 17 Issue: 2 Pages: 1-12

    • DOI

      10.1002/jbio.202300166

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced periodontal tissue healing via vascular endothelial growth factor expression following low‐level erbium‐doped: yttrium, aluminum, and garnet laser irradiation: In vitro and in vivo studies2023

    • Author(s)
      Takemura Shu、Mizutani Koji、Mikami Risako、Nakagawa Keita、Hakariya Masahiro、Sakaniwa Eri、Saito Natsumi、Kominato Hiromi、Kido Daisuke、Takeda Kohei、Aoki Akira、Iwata Takanori
    • Journal Title

      Journal of Periodontology

      Volume: - Issue: 9 Pages: 1-14

    • DOI

      10.1002/jper.23-0458

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of various light-emitting diode wavelengths on periodontopathic bacteria and gingival fibroblasts: An in vitro study2023

    • Author(s)
      Hayashi Sakura、Takeuchi Yasuo、Hiratsuka Koichi、Kitanaka Yutaro、Toyoshima Keita、Nemoto Takashi、Aung Nay、Hakariya Masahiro、Ikeda Yuichi、Iwata Takanori、Aoki Akira
    • Journal Title

      Photodiagnosis and Photodynamic Therapy

      Volume: 44 Pages: 103860-103860

    • DOI

      10.1016/j.pdpdt.2023.103860

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Influence of Reactive Oxygen Species on Wound Healing and Tissue Regeneration in Periodontal and Peri-Implant Tissues in Diabetic Patients2023

    • Author(s)
      Buranasin Prima、Kominato Hiromi、Mizutani Koji、Mikami Risako、Saito Natsumi、Takeda Kohei、Iwata Takanori
    • Journal Title

      Antioxidants

      Volume: 12 Issue: 9 Pages: 1787-1787

    • DOI

      10.3390/antiox12091787

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antibacterial activity of lysozyme‐chitosan oligosaccharide conjugates on two periodontal bacteria2023

    • Author(s)
      Takeuchi Yasuo、Nemoto Takashi、Kitanaka Yutaro、Aoki Akira、Izumi Yuichi、Iwata Takanori、Arakawa Shinichi
    • Journal Title

      Oral Diseases

      Volume: - Issue: 4 Pages: 2728-2735

    • DOI

      10.1111/odi.14710

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homemade blenderized tube feeding improves gut microbiome communities in children with enteral nutrition2023

    • Author(s)
      Katagiri S, Ohsugi Y, Shiba T, Yoshimi K, Nakagawa K, Nagasawa Y, Uchida A, Liu A, Lin P, Tsukahara Y, Iwata T, Tohara H.
    • Journal Title

      Frontiers in Microbiology

      Volume: 14 Pages: 1-14

    • DOI

      10.3389/fmicb.2023.1215236

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Malnutrition- inflammation- atherosclerosis (MIA) syndrome associates with periodontitis in end-stage renal disease patients undergoing hemodialysis: a cross-sectional study2023

    • Author(s)
      Mikami Risako、Mizutani Koji、Gohda Tomohito、Matsuyama Yusuke、Gotoh Hiromichi、Nakagawa Keita、Takemura Shu、Aoyama Norio、Matsuura Takanori、Kido Daisuke、Takeda Kohei、Saito Natsumi、Izumi Yuichi、Iwata Takanori
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 11805-11805

    • DOI

      10.1038/s41598-023-38959-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peri-implantitis management by resective surgery combined with implantoplasty and Er:YAG laser irradiation, accompanied by free gingival graft: a case report2023

    • Author(s)
      Shiba Takahiko、Komatsu Keiji、Watanabe Takayasu、Takeuchi Yasuo、Nemoto Takashi、Ohsugi Yujin、Katagiri Sayaka、Shimogishi Masahiro、Marukawa Eriko、Iwata Takanori
    • Journal Title

      Therapeutic Advances in Chronic Disease

      Volume: 14 Pages: 1-13

    • DOI

      10.1177/20406223231174816

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel and Efficient Method for Diagnosing Infective Endocarditis Using 16S Ribosomal RNA Gene Amplicon Sequence2023

    • Author(s)
      Kataoka Akihisa、Shiba Takahiko、Katagiri Sayaka、Koyama Shuhei、Kito Kento、Ota Tatsuya、Katayama Taiga、Ohsugi Yujin、Nagai Takahiko、Kobayashi Ryota、Komatsu Keiji、Urata Masahiro、Imazuru Tomohiro、Iwata Takanori、Kozuma Ken
    • Journal Title

      JACC: Case Reports

      Volume: 11 Pages: 101793-101793

    • DOI

      10.1016/j.jaccas.2023.101793

    • URL

      https://pure.teikyo.jp/en/publications/50a6924b-47b3-43ca-8e4d-590b59878f05

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Periodontitis was associated with worse clinical outcomes after catheter ablation for paroxysmal atrial fibrillation2023

    • Author(s)
      Tashiro Akira、Yonetsu Taishi、Aoyama Norio、Shiheido-Watanabe Yuka、Niida Takayuki、Miyazaki Shinsuke、Maejima Yasuhiro、Goya Masahiko、Isobe Mitsuaki、Iwata Takanori、Sasano Tetsuo
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 9

    • DOI

      10.3389/fcvm.2022.1061243

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-inflammatory effects of cold atmospheric plasma irradiation on the THP-1 human acute monocytic leukemia cell line2023

    • Author(s)
      Hirasawa Ito、Odagiri Haruka、Park Giri、Sanghavi Rutvi、Oshita Takaya、Togi Akiko、Yoshikawa Katsunori、Mizutani Koji、Takeuchi Yasuo、Kobayashi Hiroaki、Katagiri Sayaka、Iwata Takanori、Aoki Akira
    • Journal Title

      PLOS ONE

      Volume: 18 Issue: 10 Pages: 1-15

    • DOI

      10.1371/journal.pone.0292267

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Mobility of Polyrotaxane Surfaces Alleviates Oxidative Stress‐Induced Senescence in Mesenchymal Stem Cells2023

    • Author(s)
      Masuda Hiroki、Arisaka Yoshinori、Hakariya Masahiro、Iwata Takanori、Yoda Tetsuya、Yui Nobuhiko
    • Journal Title

      Macromolecular Bioscience

      Volume: 23 Issue: 5

    • DOI

      10.1002/mabi.202300053

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Morphological analysis of the impact of diabetes on gingival capillaries with non-invasive blood flow scope ? A preliminary study2022

    • Author(s)
      Takeda Kohei、Mizutani Koji、Mikami Risako、Fujino Aiko、Ito Yuri、Takeuchi Shunsuke、Saito Natsumi、Iwata Takanori
    • Journal Title

      Journal of Dental Sciences

      Volume: 10 Issue: 3 Pages: 024-024

    • DOI

      10.1016/j.jds.2022.10.024

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficient reprogramming of human fibroblasts using RNA reprogramming with DAPT and iDOT1L under normoxia conditions2022

    • Author(s)
      Morita Kazuki、Nakamura Akihiro、Machida Masakazu、Kawasaki Tomoyuki、Nakanishi Rina、Ichida Justin、Iwata Takanori、Umezawa Akihiro、Akutsu Hidenori
    • Journal Title

      Regenerative Therapy

      Volume: 21 Pages: 389-397

    • DOI

      10.1016/j.reth.2022.09.002

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High‐frequency pulsed diode laser irradiation inhibits bone resorption in mice with ligature‐induced periodontitis2022

    • Author(s)
      Ohsugi Yujin、Hatasa Masahiro、Katagiri Sayaka、Hirota Tomomitsu、Shimohira Tsuyoshi、Shiba Takahiko、Komatsu Keiji、Tsuchiya Yosuke、Fukuba Shunsuke、Lin Peiya、Toyoshima Keita、Maekawa Shogo、Niimi Hiromi、Iwata Takanori、Aoki Akira
    • Journal Title

      Journal of Clinical Periodontology

      Volume: 49 Issue: 12 Pages: 1275-1288

    • DOI

      10.1111/jcpe.13695

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic factors affecting periodontal regenerative therapy using recombinant human fibroblast growth factor-2: A 3-year cohort study2022

    • Author(s)
      Mikami Risako、Sudo Takeaki、Fukuba Shunsuke、Takeda Kohei、Matsuura Takanori、Kariya Tomoaki、Takeuchi Shunsuke、Ochiai Akane、Kawamoto Sakurako、Toyoshima Keita、Mizutani Koji、Arakawa Shinichi、Aoki Akira、Iwata Takanori
    • Journal Title

      Regenerative Therapy

      Volume: 21 Pages: 271-276

    • DOI

      10.1016/j.reth.2022.07.006

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppressed Migration and Enhanced Cisplatin Chemosensitivity in Human Cancer Cell Lines by Tuning the Molecular Mobility of Supramolecular Biomaterials2022

    • Author(s)
      Hakariya Masahiro、Arisaka Yoshinori、Masuda Hiroki、Yoda Tetsuya、Iwata Takanori、Yui Nobuhiko
    • Journal Title

      Macromolecular Bioscience

      Volume: 23 Issue: 2 Pages: 2200438-2200438

    • DOI

      10.1002/mabi.202200438

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Independent Roles of Molecular Mobility and Zeta Potential on Supramolecular Surfaces in the Sequence of RAW264.7 Macrophage Responses2022

    • Author(s)
      Tanaka‐Takemura Yuka、Arisaka Yoshinori、Hakariya Masahiro、Masuda Hiroki、Mikami Ryo、Sekiya‐Aoyama Ruriko、Iwata Takanori、Yoda Tetsuya、Ono Takashi、Yui Nobuhiko
    • Journal Title

      Macromolecular Bioscience

      Volume: 22 Issue: 11 Pages: 2200282-2200282

    • DOI

      10.1002/mabi.202200282

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Association of type 2 diabetes with periodontitis and tooth loss in patients undergoing hemodialysis2022

    • Author(s)
      Mikami Risako、Mizutani Koji、Matsuyama Yusuke、Gohda Tomohito、Gotoh Hiromichi、Aoyama Norio、Matsuura Takanori、Kido Daisuke、Takeda Kohei、Saito Natsumi、Fujiwara Takeo、Izumi Yuichi、Iwata Takanori
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 5 Pages: e0267494-e0267494

    • DOI

      10.1371/journal.pone.0267494

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel flapless esthetic procedure for the elimination of extended gingival metal tattoos adjacent to prosthetic teeth: Er:YAG laser micro-keyhole surgery2022

    • Author(s)
      Mizutani Koji、Mikami Risako、Tsukui Akira、Nagai Shigeyuki、Pavlic Verica、Komada Wataru、Iwata Takanori、Aoki Akira
    • Journal Title

      Journal of Prosthodontic Research

      Volume: 66 Issue: 2 Pages: 346-352

    • DOI

      10.2186/jpr.JPR_D_21_00045

    • NAID

      130008089849

    • ISSN
      1883-1958, 1883-9207
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Single cell RNA sequencing reveals critical functions of Mkx in periodontal ligament homeostasis.2022

    • Author(s)
      Takada K, Chiba T, Miyazaki T, Yagasaki L, Nakamichi R, Iwata T, Moriyama K, Harada H, Asahara H.
    • Journal Title

      Front Cell Dev Biol

      Volume: 4 Pages: 1-13

    • DOI

      10.3389/fcell.2022.795441

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of the bone graft materials used for guided bone regeneration on subsequent peri-implant inflammation: an experimental ligature-induced peri-implantitis model in Beagle dogs2022

    • Author(s)
      Sato Ryo、Matsuura Takanori、Akizuki Tatsuya、Fukuba Shunsuke、Okada Munehiro、Nohara Kohei、Takeuchi Shunsuke、Hoshi Shu、Ono Wataru、Maruyama Kiichi、Izumi Yuichi、Iwata Takanori
    • Journal Title

      International Journal of Implant Dentistry

      Volume: 8 Issue: 1

    • DOI

      10.1186/s40729-022-00403-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment of Peri-implantitis Caused by Malpositioning and an Extra Implant: A Case Report2022

    • Author(s)
      Shiba Takahiko、Katagiri Sayaka、Komatsu Keiji、Nemoto Takashi、Takeuchi Yasuo、Chen Bo、Zhou Yongsheng、Iwata Takanori
    • Journal Title

      The International Journal of Periodontics & Restorative Dentistry

      Volume: 42 Issue: 1 Pages: e15-e20

    • DOI

      10.11607/prd.4800

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired dental implant osseointegration in rat with streptozotocin‐induced diabetes2022

    • Author(s)
      Saito Natsumi、Mikami Risako、Mizutani Koji、Takeda Kohei、Kominato Hiromi、Kido Daisuke、Ikeda Yuichi、Buranasin Prima、Nakagawa Keita、Takemura Shu、Ueno Takeshi、Hosaka Keiichi、Hanawa Takao、Shinomura Tamayuki、Iwata Takanori
    • Journal Title

      Journal of Periodontal Research

      Volume: 57 Issue: 2 Pages: 412-424

    • DOI

      10.1111/jre.12972

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research

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Published: 2022-04-19   Modified: 2024-12-25  

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