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Bone regeneration with cell-derived factors in response to severe culture environment

Research Project

Project/Area Number 16H05540
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionNagoya University

Principal Investigator

Hibi Hideharu  名古屋大学, 医学系研究科, 教授 (90345885)

Co-Investigator(Kenkyū-buntansha) 黒田 健介  名古屋大学, 未来材料・システム研究所, 准教授 (00283408)
土屋 周平  名古屋大学, 医学部附属病院, 助教 (20569785)
興戸 正純  名古屋大学, 未来材料・システム研究所, 教授 (50126843)
片桐 渉  名古屋大学, 医学系研究科, 講師 (10437030)
山本 朗仁  名古屋大学, 医学系研究科, 准教授 (50244083)
Research Collaborator YAMAMOTO akihito  徳島大学, 医歯薬学研究部, 教授 (50244083)
KATAGIRI wataru  新潟大学, 医歯学総合研究科, 准教授 (10437030)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2016: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Keywords移植・再生医療 / 再生医学 / 歯学
Outline of Final Research Achievements

Stimulation of stem cells by hypoxia or mechanical stress promoted gene expression related to osteogenesis and angiogenesis and increased the amount of protein resulting from them in the cell-conditioned media. The application of the conditioned media to various tissue defect and inflammatory tissue injury models controled inflammation, repaired and regenerated the tissue. The mechanism was that localized macrophages were oppositely polarized and locally mobilized tissue forming cells constructed a vascular network and repaired or formed compatible tissue. We identified the growth factors and substrates contained in the conditioned media, clarified the optimal combination of them according to the target function, and showed that they actually repaired or regenerated the tissue in experimental animal models.

Academic Significance and Societal Importance of the Research Achievements

幹細胞は培養環境が過酷なほどそれに適応し生存しようとしてさまざまな基質や因子群を生成し,それらが培養上清中には含まれる.これらが炎症を制御し組織を修復あるいは適合組織を再生させる効果は因子群では単独因子と比べて極めて低濃度で得られており,この理由は生体内の複雑な組織修復および形成過程を並行的かつ連続的に進めているからであり,この効能は効率的なだけでなく生理的でもあると考えられる.さらに目的とする機能別に有効な因子群を明らかにでき,製剤化および創薬への途を開いた.以上の方法は培養細胞を生体内に導入する従来の再生医療と比べて,調節性,安全性,普遍性の点で優れ,時間的,経済的に有利であると考える.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (33 results)

All 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (22 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] A Mouse Distraction Osteogenesis Model2018

    • Author(s)
      Fujio Masahito、Osawa Yusuke、Matsushita Masaki、Ogisu Kota、Tsuchiya Shuhei、Kitoh Hiroshi、Hibi Hideharu
    • Journal Title

      Journal of Visualized Experiments

      Volume: 141 Issue: 141 Pages: 0-0

    • DOI

      10.3791/57925

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dental pulp-derived stem cell conditioned medium to regenerate peripheral nerves in a novel animal model of dysphagia2018

    • Author(s)
      Tsuruta Takeshi、Sakai Kiyoshi、Watanabe Junna、Katagiri Wataru、Hibi Hideharu
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 12 Pages: e0208938-e0208938

    • DOI

      10.1371/journal.pone.0208938

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kaempferol-immobilized titanium dioxide promotes formation of new bone: effects of loading methods on bone marrow stromal cell differentiation in vivo and in vitro2018

    • Author(s)
      S. Tsuchiya, K. Sugimoto, H. Kamio, K. Okabe, K. Kuroda, M. Okido, H. Hibi
    • Journal Title

      International Journal of Nanomedicine

      Volume: 13 Pages: 1665-1676

    • DOI

      10.2147/ijn.s150786

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Secretomes from mesenchymal stem cells participate in the regulation of osteoclastogenesis in vitro2017

    • Author(s)
      Ogata K, Katagiri W, Hibi H
    • Journal Title

      Clinical Oral Investigations

      Volume: 21 Issue: 6 Pages: 1979-1988

    • DOI

      10.1007/s00784-016-1986-x

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity2017

    • Author(s)
      Kano, F. Matsubara, K. Ueda, M. Hibi, H. Yamamoto, A.
    • Journal Title

      Stem Cells

      Volume: 3 Issue: 3 Pages: 641-653

    • DOI

      10.1002/stem.2534

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A defined mix of cytokines mimics conditioned medium from cultures of bone marrow-derived mesenchymal stem cells and elicits bone regeneration2017

    • Author(s)
      Katagiri W, Sakaguchi K, Kawai T, Wakayama Y, Osugi M, Hibi H
    • Journal Title

      Cell Proliferation

      Volume: in press Issue: 3

    • DOI

      10.1111/cpr.12333

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Secreted ectodomain of SIGLEC-9 and MCP-1 synergistically improve acute liver failure in rats by altering macrophage polarity2017

    • Author(s)
      Ito T, Ishigami M, Matsushita Y, Hirata M, Matsubara K, Ishikawa T, Hibi H, Ueda M, Hirooka Y, Goto H, Yamamoto A
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 44043-44043

    • DOI

      10.1038/srep44043

    • NAID

      120006306638

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical study of bone regeneration by conditioned medium from mesenchymal stem cells after maxillary sinus floor elevation2017

    • Author(s)
      Katagiri W, Watanabe J, Toyama N, Osugi M, Sakaguchi K, Hibi H
    • Journal Title

      Implant Dentistry

      Volume: 26 Issue: 4 Pages: 607-612

    • DOI

      10.1097/id.0000000000000618

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Periodontal tissue regeneration using the cytokine cocktail mimicking secretomes in the conditioned media from human mesenchymal stem cells2017

    • Author(s)
      Sakaguchi K, Katagiri W, Osugi M, Kawai T, Sugimura-Wakayama Y, Hibi H
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 26 Issue: 1 Pages: 100-106

    • DOI

      10.1016/j.bbrc.2017.01.065

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic analysis of bone proteins adsorbed onto the surface of titanium dioxide2016

    • Author(s)
      K. Sugimoto, S. Tsuchiya, M. Omori, R. Matsuda, M. Fujio, K. Kuroda,Okido, H. Hibi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 7 Pages: 316-322

    • DOI

      10.1016/j.bbrep.2016.07.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] M2マクロファージ誘導因子MCP-1/sSiglec9を用いた骨再生効果の検討2019

    • Author(s)
      石川純,加納史也,竹内千明,松下嘉泰,渡邉和代,日比英晴,山本朗仁
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Role of regenerative medicine in medical treatment2018

    • Author(s)
      Hibi H
    • Organizer
      The 66th Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ビスホスホネート関連顎骨壊死に対する間葉系幹細胞由来エクソソームを用いた治療の可能性2018

    • Author(s)
      渡邊純奈,酒井陽,岡部一登,若山有紀子,坂口晃平,鶴田剛士,日比英晴
    • Organizer
      第72回日本口腔科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 間葉系幹細胞培養上清を模した液性因子カクテル剤を用いた薬剤関連顎骨壊死の新規治療法の検討2018

    • Author(s)
      緒方謙一,森山雅文,松村万由,片桐渉,日比英晴,中村誠司
    • Organizer
      第72回日本口腔科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effects of mesenchymal stem cell-derived exosomes for rat BRONJ model2018

    • Author(s)
      Watanabe J, Sakai K, Okabe K, Sugimura Y, Sakaguchi K, Tsuruta T, Hibi H
    • Organizer
      96th General Session & Exhibition of the IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exosomes derived from mesenchymal stem cells enhanced bone regeneration2018

    • Author(s)
      Sakaguchi K, Sakai K, Sugimura Y, Tsuruta T, Watanabe J, Katagiri W, Hibi H
    • Organizer
      96th General Session & Exhibition of the IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel approach to peripheral nerve regeneration using conditioned media2018

    • Author(s)
      Sugimura Y, Wakayama H, Sakaguchi K. Tsuruta T, Watanabe J, Katagiri W, Hibi H
    • Organizer
      96th General Session & Exhibition of the IADR
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] BRONJ 発症におけるエクソソームの効果の検討2018

    • Author(s)
      渡邊純奈,酒井陽,日比英晴
    • Organizer
      第60回歯科基礎医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 伸展刺激下で得た細胞培養上清における骨形成能の検討2018

    • Author(s)
      荻須宏太,藤尾正人,土屋周平,神尾尚伸,外山直人,日比英晴
    • Organizer
      第63回日本口腔外科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 間葉系幹細胞由来エクソソームを用いた BRONJに対する治療の有効性の検討2018

    • Author(s)
      渡邊純奈,酒井陽,岡部一登,椙村有紀子,坂口晃平,鶴田剛士,中道瑛司,日比英晴
    • Organizer
      第63回日本口腔外科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨髄間葉系幹細胞が分泌するエクソソームによる新規骨再生法2018

    • Author(s)
      坂口晃平,酒井陽,椙村有紀子,鶴田剛士,渡邊純奈,片桐渉,日比英晴
    • Organizer
      第63回日本口腔外科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] チタン表面の大気圧プラズマ処理がマクロファージの挙動におよぼす影響の検討2018

    • Author(s)
      外山直人,土屋周平,原憲史,藤尾正人,岡部一登,佐世暁,荻須宏太,神尾尚伸,日比英晴
    • Organizer
      第63回日本口腔外科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 骨髄由来間葉系幹細胞が分泌するエクソソームによる新たな骨再生2018

    • Author(s)
      坂口晃平,酒井陽,片桐渉,若山有紀子,鶴田剛士,渡邊純奈,日比英晴
    • Organizer
      第17回日本再生医療学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Secreted ectodomain of sialic acid-binding immunoglobulin-like lectin-9 and monocyte chemoattractant protein-1 derived from dental pulp stem cells synergistically regenerate transected rat peripheral nerves by altering macrophage polarity2017

    • Author(s)
      Kano F, Yamamoto A, Matsubara K, Hibi H
    • Organizer
      23rd International Conference on Oral and Maxillofacial Surgeons
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラット末梢性嚥下障害モデルを用いた乳歯歯髄幹細胞由来成長因子の治療効果の検討2017

    • Author(s)
      鶴田剛士,片桐渉,大杉将嗣,酒井陽,若山有紀子,坂口晃平,渡邊純奈,日比英晴
    • Organizer
      第71回日本口腔科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] MCP-1 と sSiglec-9 はマクロファージの極性変化を介して骨再生を促進する2017

    • Author(s)
      加納史也,山本朗仁,石川純,市村典久,日比英晴
    • Organizer
      第62回日本口腔外科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 乳歯歯髄幹細胞由来成長因子は神経の血管新生を介してラット末梢性嚥下障害を改善する2017

    • Author(s)
      鶴田剛士,酒井陽,片桐渉,大杉将嗣,椙村有紀子,坂口晃平,渡邊純奈,日比英晴
    • Organizer
      第62回日本口腔外科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 乳歯歯髄幹細胞由来培養上清を用いた末梢神経再生治療の検討2017

    • Author(s)
      椙村有紀子,酒井陽,坂口晃平,鶴田剛士,渡邊純奈,片桐渉,日比英晴
    • Organizer
      第62回日本口腔外科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 他家骨髄由来間葉系細胞の移植による骨再生の検討2017

    • Author(s)
      渡邊純奈,片桐渉,大杉将嗣,酒井陽,岡部一登,椙村有紀子,坂口晃平,鶴田剛士,外山直人,日比英晴
    • Organizer
      第38回日本口腔インプラント学会中部支部学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 骨髄間葉系幹細胞由来培養上清を模倣した成長因子混合剤による歯周組織再生2016

    • Author(s)
      坂口晃平,片桐渉,大杉将嗣,酒井陽,椙村有紀子,鶴田剛士,渡邊純奈,日比英晴
    • Organizer
      第61回日本口腔外科学会
    • Place of Presentation
      幕張メッセ(千葉県千葉市)
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] インプラント周囲の骨形成促進を目指したチタン表面へのケンフェロールの応用2016

    • Author(s)
      杉本圭佑,土屋周平,原憲史,藤尾正人,松下嘉泰,松田亮,佐世暁,日比英晴
    • Organizer
      日本補綴歯科学会第125回学術大会
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Kaempferolを用いた新規骨補填材料の開発2016

    • Author(s)
      松下嘉泰,土屋周平,原憲史,藤尾正人,杉本圭佑,松田亮,佐世暁,日比英晴
    • Organizer
      日本補綴歯科学会第125回学術大会
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Related Report
      2016 Annual Research Report
  • [Book] The Sinus Bone Graft, Third Edition2019

    • Author(s)
      Hibi H, Katagiri W, Tsuchiya S, Omori M, Ueda M
    • Total Pages
      288
    • Publisher
      Quintessence Publishing
    • ISBN
      9780867157918
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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