Development of the method for bone regeneration mimicing distraction osteogenesis for extensive bone defects without distraction devices

• Project/Area Number: 25293408
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Nagoya University
• Principal Investigator: HIBI Hideharu 名古屋大学, 医学(系)研究科(研究院), 教授 (90345885)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Akihito 名古屋大学, 大学院医学系研究科, 准教授 (50244083) ; KURODA Kensuke 名古屋大学, 未来材料・システム研究所, 准教授 (00283408) ; KATAGIRI Wataru 名古屋大学, 大学院医学系研究科, 講師 (10437030) ; HATTORI Hisashi 名古屋大学, 医学部附属病院, 講師 (60332699) ; TSUCHIYA Shuhei 名古屋大学, 医学部附属病院, 助教 (20569785)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
• Keywords: 移植・再生医療 / 再生医学 / 骨再生 / 幹細胞培養上清

Outline of Final Research Achievements

The components of the conditioned media collected from bone marrow mesenchymal stem cells and dental pulp stem cells were detected and partially quantified. We showed that the conditioned media enhanced cell adhesion ability, cell migration ability, angiogenic potential, anti-inflammatory action and anti-apoptotic effect, and that the conditioned media from hypoxic-cultured cells further enhanced the cell migration ability and the angiogenic potential in vitro. We also showed that the conditioned media promoted vascular network formation and consequent bone regeneration, and that the conditioned media from hypoxic-cultured cells further promoted this process in vivo.

Research Products

• [Int'l Joint Research] University of Bergen(Norway)
• [Journal Article] Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis. (2016)
  • Author(s): Ishikawa J, Takahashi N, Matsumoto T, Yoshioka Y, Yamamoto N, Nishikawa M, Hibi H, Ishigro N, Ueda M, Furukawa K, Yamamoto A.
  • Journal Title: Bone. Volume: 83 Pages: 210-219
  • DOI: 10.1016/j.bone.2015.11.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] CD109 is a component of exosome secreted from cultured cells (2016)
  • Author(s): Sakakura H, Mii S, Hagiwara S, Kato T, Yamamoto N, Hibi H, Takahashi M, Murakumo Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 469 Issue: 4 Pages: 816-822
  • DOI: 10.1016/j.bbrc.2015.12.063
  • Peer Reviewed / Open Access
• [Journal Article] Clinical review of bone regenerative medicine and maxillomandibular reconstruction (2016)
  • Author(s): Hibi H
  • Journal Title: Oral Science International Volume: 13 Issue: 1 Pages: 15-19
  • DOI: 10.1016/s1348-8643(15)00037-3
  • NAID: 130005137546
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells (2016)
  • Author(s): Katagiri W, Osugi M, Kawai T, Hibi H
  • Journal Title: Head & Face Medicine Volume: 12 Issue: 1 Pages: 5-5
  • DOI: 10.1186/s13005-016-0101-5
  • Peer Reviewed / Open Access
• [Journal Article] A new application of cell-free bone regeneration: Immobilizing stem cells from human exfoliated deciduous teeth-conditioned medium onto titanium implants by using atmospheric pressure plasma treatment (2015)
  • Author(s): Masahiro Omori, Shuhei Tsuchiya, Kenji Hara, Kensuke Kuroda, Hideharu Hibi, Masazumi Okido and Minoru Ueda
  • Journal Title: Stem Cell Research & Therapy Volume: 6 Issue: 1 Pages: 124-136
  • DOI: 10.1186/s13287-015-0114-1
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Peripheral nerve regeneration by secretomes of stem cells from human exfoliated deciduous teeth (2015)
  • Author(s): Sugimura-Wakayama Y, Katagiri W, Osugi M, Kawai T, Ogata K, Sakaguchi K, Hibi H
  • Journal Title: Stem Cells and Development Volume: 24 Issue: 22 Pages: 2687-2699
  • DOI: 10.1089/scd.2015.0104
  • Peer Reviewed
• [Journal Article] Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of alzheimer’s disease. (2015)
  • Author(s): Mita T, Furukawa-Hibi Y, Takeuchi H, Hattori H, Yamada K, Hibi H, Ueda M, Yamamoto A.
  • Journal Title: Behav Brain Res. Volume: 293 Pages: 189-197
  • DOI: 10.1016/j.bbr.2015.07.043
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An experimental study on guided bone regeneration by using a polylactide-co-glycolide membrane-immobilized conditioned medium (2015)
  • Author(s): Tsuchiya S, Omori M, Hara K, Fujio M, Ikeno M, Hibi H, Ueda M
  • Journal Title: International Journal of Oral and Maxillofacial Implants Volume: 30 Issue: 5 Pages: 1175-86
  • DOI: 10.11607/jomi.3915
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Secreted Frizzled-Related Protein Promotes Bone Regeneration by Human Bone Marrow-Derived Mesenchymal Stem Cells (2015)
  • Author(s): Katagiri W, Osugi M, Kawai T, Hibi H
  • Journal Title: International Journal of Molecular Science Volume: 16 Issue: 10 Pages: 23250-23258
  • DOI: 10.3390/ijms161023250
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Conditioned medium from mesenchymal stem cells enhances early bone regeneration after maxillary sinus floor elevation in rabbits (2015)
  • Author(s): Katagiri W, Osugi M, Kinoshita K, Hibi H
  • Journal Title: Implant dentistry Volume: 24 Issue: 6 Pages: 657-663
  • DOI: 10.1097/id.0000000000000335
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function (2015)
  • Author(s): Izumoto-Akita T, Tsunekawa S, Yamamoto A, Uenishi E, Ishikawa K, Ogata H, Iida A, Ikeniwa M, Hosokawa K, Niwa Y, Maekawa R, Yamauchi Y, Seino Y, Hamada Y, Hibi H, Arima H, Ueda M, Oiso Y
  • Journal Title: BMJ Open Diabetes Research & Care Volume: 3 Issue: 1 Pages: e000128-e000128
  • DOI: 10.1136/bmjdrc-2015-000128
  • Peer Reviewed / Open Access
• [Journal Article] Dental pulp-derived stem cell conditioned medium reduces cardiac injury following ischemia-reperfusion (2015)
  • Author(s): Yamaguchi S, Shibata R, Yamamoto N, Nishikawa M, Hibi H, Tanigawa T, Ueda M, Murohara T, Yamamoto A
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 16295-16295
  • DOI: 10.1038/srep16295
  • Peer Reviewed / Open Access
• [Journal Article] Conditioned media from hypoxic-cultured human dental pulp cells promotes bone healing during distraction osteogenesis (2015)
  • Author(s): Fujio M, Xing Z, Sharabi N, Xue Y, Yamamoto A, Hibi H, Ueda M, Fristad I, Mustafa K
  • Journal Title: Journal of Tissue Engineering and Regenerative Medicine Volume: Epub ahead of print Issue: 7 Pages: 230-240
  • DOI: 10.1002/term.2109
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration (2015)
  • Author(s): Kawai, T., Katagiri, W., Osugi, M., Sugimura, Y., Hibi, H., Ueda, M.
  • Journal Title: Cytotherapy Volume: 17 Issue: 4 Pages: 369-381
  • DOI: 10.1016/j.jcyt.2014.11.009
  • Peer Reviewed
• [Journal Article] Evaluation of the therapeutic effects of conditioned media from mesenchymal stem cells in a rat bisphosphonate-related osteonecrosis of the jaw-like model (2015)
  • Author(s): Ogata, K., Katagiri, W., Osugi, M., Kawai, T., Sugimura, Y., Hibi, H., Nakamura, S., Ueda, M.
  • Journal Title: Bone Volume: 74 Pages: 95-105
  • DOI: 10.1016/j.bone.2015.01.011
  • Peer Reviewed
• [Journal Article] Stem cell-conditioned medium accelerates distraction osteogenesis through multiple regenerative mechanisms (2014)
  • Author(s): Ando K, Matsubara K, Ishikawa J, Fujio M, Shohara R, Hibi H, Ueda M, Yamamoto A
  • Journal Title: Bone Volume: 61 Pages: 82-90
  • DOI: 10.1016/j.bone.2013.12.029
  • Peer Reviewed
• [Presentation] 骨髄由来間葉系幹細胞培養上清由来液性因子を用いた新たな骨再生治療に関する臨床的検討 (2016)
  • Author(s): 外山直人，片桐渉，大杉将嗣，安藤さやか，若山有紀子，坂口晃平，鶴田剛士，渡邊純奈，日比英晴
  • Organizer: 第15回日本再生医療学会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] イヌ歯周病モデルを用いた成長因子混合剤による歯周組織再生能の検討 (2016)
  • Author(s): 坂口晃平，片桐渉，大杉将嗣，若山有紀子，鶴田剛士，日比英晴
  • Organizer: 第15回日本再生医療学会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-03-17
• [Presentation] Conditioned media from bone marrow derived mesenchymal stem cells enhances bone regeneration in rat calvarial bone defects (2016)
  • Author(s): Osugi M, Katagiri W, Sakaguchi K, Kawai T, Hibi H
  • Organizer: Annual Meeting of Academy of Osseointegration
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2016-02-17
  • Int'l Joint Research
• [Presentation] Clinical study for bone regeneration after maxillary sinus floor elevation by secretomes from mesenchymal stem cells (2016)
  • Author(s): Katagiri W, Osugi M, Watanabe J, Sakaguchi K, Hibi H
  • Organizer: Annual Meeting of Academy of Osseointegration
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2016-02-17
  • Int'l Joint Research
• [Presentation] ヒト歯髄幹細胞無血清培養上清を用いた関節炎モデルマウスにおける治療効果の検討 (2015)
  • Author(s): 石川純，山本憲幸，西川雅也，若山博隆，山口聡，日比英晴，山本朗仁
  • Organizer: 第60回日本口腔外科学会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-16
• [Presentation] 幹細胞培養上清由来液性因子を用いた新規骨再生医療における組織学的検討 (2015)
  • Author(s): 渡邊純奈，片桐渉，大杉将嗣，安藤さやか，椙村有紀子，緒方謙一，坂口晃平，鶴田剛士，日比英晴
  • Organizer: 第60回日本口腔外科学会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-16
• [Presentation] ヒト歯髄幹細胞無血清培養上清を用いた関節炎モデルマウスにおける治療効果の検討 (2015)
  • Author(s): 石川純，高橋伸典，山本憲幸，西川雅也，若山博隆，山口聡，日比英晴，石黒直樹，山本朗仁
  • Organizer: 第36回日本炎症・再生医学会
  • Place of Presentation: 虎の門ヒルズフォーラム（東京都港区）
  • Year and Date: 2015-07-21
• [Presentation] 成長因子混合剤による新たな骨再生法 (2015)
  • Author(s): 坂口晃平，片桐渉，大杉将嗣，河合孝真，椙村有紀子，緒方謙一，日比英晴
  • Organizer: 第14回日本再生医療学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-03-21
• [Presentation] ラットBRONJ様モデルにおける幹細胞培養上清による治療効果の検討 (2015)
  • Author(s): 緒方謙一，片桐渉，大杉将嗣，河合孝真，椙村有紀子，坂口晃平，日比英晴，中村誠司，上田実
  • Organizer: 第14回日本再生医療学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2015-03-19
• [Presentation] Novel Bone Regenerative Medicine Using the Secretomes From Bone Marrow-derived Mesenchymal Stem Cells (2015)
  • Author(s): Katagiri, W., Sugimura, Y., Osugi, M., Kawai, T., Ogata, K., Sakaguchi, K., Hibi, H
  • Organizer: IADR/AADR/CADR General Session
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-03-12
• [Presentation] Conditioned Media From SHED Enhanced Peripheral Nerve Regeneration (2015)
  • Author(s): Sugimura, Y., Katagiri, W., Osugi, M., Kawai, T., Ogata, K., Sakaguchi, K., Hibi, H.
  • Organizer: IADR/AADR/CADR General Session
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-03-12
• [Presentation] ラットBRONJ様モデルにおける幹細胞培養上清由来液性因子による治療効果の検討 (2014)
  • Author(s): 緒方謙一，片桐渉，大杉将嗣，河合孝真，椙村有紀子，坂口晃平，日比英晴，中村誠司，上田実
  • Organizer: 第59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: 2014-10-18
• [Presentation] 大気圧プラズマ処理したチタンインプラントへのヒト脱落乳歯幹細胞由来培養上清の応用 (2014)
  • Author(s): 大森正裕，土屋周平，原憲史，藤尾正人，西野雄大，杉本圭佑，日比英晴，上田実
  • Organizer: 第59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: 2014-10-17
• [Presentation] 乳歯歯髄幹細胞を用いた末梢神経再生治療の可能性 (2014)
  • Author(s): 椙村有紀子，片桐渉，大杉将嗣，河合孝真，緒方謙一，坂口晃平，日比英晴，上田実
  • Organizer: 第59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: 2014-10-17
• [Presentation] Evaluation of the therapeutic effects of conditioned media from mesenchymal stem cells in rat bisphosphonate-related osteonecrosis of the jaw model (2014)
  • Author(s): Ogata, K., Katagiri, W., Osugi, M., Kawai, T., Sugimura, Y., Sakaguchi, K., Hibi, H., Nakamura, S., Ueda, M.
  • Organizer: 23rd Annual Scientific Meeting of European Association for Osseointegration
  • Place of Presentation: Rome, Italy
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Novel strategy of bone regeneration with the cocktail of recombinant cytokines mimicking secretomes derived from mesenchymal stem cells (2014)
  • Author(s): Sakaguchi, K., Katagiri, W., Osugi, M., Kawai, T., Sugimura, Y., Ogata, K., Hibi, H., Ueda, M.
  • Organizer: 23rd Annual Scientific Meeting of European Association for Osseointegration
  • Place of Presentation: Rome, Italy
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ヒト骨髄由来間葉系幹細胞の無血清培養上清による多面的な骨延長治癒促進効果の検討 (2014)
  • Author(s): 安藤友二，山本朗仁，松原弘記，石川純，藤尾正人，匠原龍太郎，日比英晴，上田実
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館（沖縄県名護市）
  • Year and Date: 2014-07-02
• [Presentation] ラットBRONJ様モデルにおける幹細胞培養上清による治療効果の検討 (2014)
  • Author(s): 緒方謙一，片桐渉，大杉将嗣，河合孝真，椙村有希子，坂口晃平，日比英晴，中村誠司，上田実
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館（沖縄県名護市）
  • Year and Date: 2014-07-02
• [Presentation] 大気圧プラズマによるチタンの親水化機能表面作製とヒト脱落乳歯幹細胞由来培養上清による骨結合の向上 (2014)
  • Author(s): 大森正裕，土屋周平，原憲史，黒田健介，日比英晴，興戸正純，上田実
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館（沖縄県名護市）
  • Year and Date: 2014-07-02
• [Presentation] 幹細胞培養上清を模した成長因子複合剤による新たな骨再生法 (2014)
  • Author(s): 坂口晃平，片桐渉，大杉将嗣，河合孝真，椙村有希子，緒方謙一，日比英晴，上田実
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館（沖縄県名護市）
  • Year and Date: 2014-07-01
• [Presentation] 骨髄由来間葉系幹細胞培養上清による歯周組織再生 (2014)
  • Author(s): 河合孝真，片桐渉，大杉将嗣，椙村有希子，緒方謙一，坂口晃平，日比英晴，上田実
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館（沖縄県名護市）
  • Year and Date: 2014-07-01
• [Presentation] オッセオインテグレーション早期獲得のためのインプラントへの細胞培養上清の応用 (2014)
  • Author(s): 土屋周平，日比英晴，上田実
  • Organizer: 第123回日本補綴歯科学会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2014-05-24
• [Presentation] 顎骨再建についての再生医学的検討 (2014)
  • Author(s): 日比英晴
  • Organizer: 第68回日本口腔科学会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-05-09
  • Invited
• [Presentation] 幹細胞培養上清由来成長因子による骨再生における血管新生 (2013)
  • Author(s): 河合孝真，片桐渉，大杉将嗣，椙村有紀子，緒方謙一，日比英晴，中村誠司，上田実
  • 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）
• [Presentation] Using hDPCs culture environments affect regenerative potential of conditioned media (2013)
  • Author(s): Fujio M, Sharabi NA, Xing Z, Xue Y, Yamamoto A, Hibi H, Ueda M, Fristad I, Mustafa KBE
  • Organizer: 46th Meeting of the Continental European Division of the International Association for Dental Research with the Scandinavian Division
  • Place of Presentation: Florence, Italy
• [Presentation] 骨髄間葉系幹細胞の無血清培養上清による骨延長の仮骨形成促進効果 (2013)
  • Author(s): 安藤友二，山本朗仁，藤尾正人，日比英晴，上田実
  • Organizer: 第43回日本口腔インプラント学会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Presentation] SDF-1の局所投与による骨再生促進効果の検討 (2013)
  • Author(s): 石川純，山本朗仁，匠原龍太郎，日比英晴，上田実
  • Organizer: 第43回日本口腔インプラント学会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Presentation] 幹細胞培養上清由来液性因子による内在性細胞の遊走および血管新生を先行させる新たな骨再生法 (2013)
  • Author(s): 片桐渉，大杉将嗣，匠原龍太郎，日比英晴，上田実
  • Organizer: 第43回日本口腔インプラント学会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Presentation] 複数のサイトカイン群による血管新生を伴う新たな骨再生法 (2013)
  • Author(s): 片桐渉，大杉将嗣，河合孝真，椙村有希子，緒方謙一，日比英晴，上田実
  • Organizer: 第58回日本口腔外科学会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Presentation] 骨髄由来間葉系幹細胞由来液性因子による歯周組織再生 (2013)
  • Author(s): 坂口晃平，片桐渉，河合孝真，大杉将嗣，椙村有希子，緒方謙一，日比英晴，上田実
  • Organizer: 第58回日本口腔外科学会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Presentation] 骨髄由来間葉系幹細胞由来液性因子による骨再生における血管新生 (2013)
  • Author(s): 大杉将嗣，片桐渉，河合孝真，椙村有希子，緒方謙一，日比英晴，上田実
  • Organizer: 第58回日本口腔外科学会
  • Place of Presentation: 福岡国際会議場（福岡市）
• [Book] Micro-Nano Mechatronics; New Trends in Material, Measurement, Control, Manufacturing and Their Applications in Biomedical Engineering (2013)
  • Author(s): Hibi H, Ueda M
  • Total Pages: 364
  • Publisher: InTech