Bone regenerative medicine by iPS cell derived soluble paracrine factors

• Project/Area Number: 15K11213
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Niigata University (2016-2017); Nagoya University (2015)
• Principal Investigator: Katagiri Wataru 新潟大学, 医歯学系, 准教授 (10437030)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 骨再生 / iPS細胞 / 増殖因子 / 培養上清 / 液性因子 / エクソソーム / 成長因子 / 骨 / サイトカイン

Outline of Final Research Achievements

Bone regeneration by the secretomes from oral mucosa derived iPS cells and bone marrow derived mesenchymal stem cells were evaluated. We used conditioned medium (CM), CM mimicked cocktail of cytokines (CC) and exosome (Exo).
CM, CC and Exo improved the migration of stem cells, angiogenesis and differentiation into osteoblast although these three did not show any statistical difference. Even in animal studies, the results of bone formation were same.
These results indicated the conditioned medium and its contents will be able to substitute the current stem cell therapy in bone regenerative medicine.

Research Products

• [Journal Article] Secretomes of mesenchymal stem cells induce early bone regeneration by accelerating migration of stem cells (2018)
  • Author(s): Ogata Kenichi、Osugi Masashi、Kawai Takamasa、Wakayama Yukiko、Sakaguchi Kohei、Nakamura Seiji、Katagiri Wataru
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 印刷中 Issue: 5 Pages: 445-451
  • DOI: 10.1016/j.ajoms.2018.04.002
  • Peer Reviewed
• [Journal Article] Clinical study of bone regeneration by conditioned medium from mesenchymal stem cells after maxillary sinus floor elevation (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells (2017)
  • Author(s): Katagiri Wataru、Kawai Takamasa、Osugi Masashi、Sugimura-Wakayama Yukiko、Sakaguchi Kohei、Kojima Taku、Kobayashi Tadaharu
  • Journal Title: Maxillofacial Plastic and Reconstructive Surgery Volume: 39 Issue: 1
  • DOI: 10.1186/s40902-017-0106-4
  • Peer Reviewed / Open Access
• [Journal Article] A defined mix of cytokines mimics conditioned medium from cultures of bone marrow-derived mesenchymal stem cells and elicits bone regeneration (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Periodontal tissue regeneration using the cytokine cocktail mimicking secretomes in the conditioned media from human mesenchymal stem cells (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Secretomes from mesenchy,al stem cells participate in the regulation of osteoclastgenesis in vitro (2017)
  • Author(s): Ogata K, Katagiri W, Hibi H
  • Journal Title: Clin Oral Investig Volume: 21(6) Pages: 1979-1988
  • Peer Reviewed
• [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 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
• [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，若山有子，鶴田剛士，渡邉純奈，日比英晴
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] New strategies for oral and maxillofacial regeneration using conditioned media and mesenchymal stem cells (2017)
  • Author(s): 片桐 渉
  • Organizer: 第62回日本口腔外科学会総会・学術大会
  • Invited
• [Presentation] Translational research in tissue engineering and regenerative medicine of bone by mesenchymal stem cells and secretomes (2017)
  • Author(s): 片桐 渉
  • Organizer: 第62回日本口腔外科学会総会・学術大会
  • Invited
• [Presentation] 骨髄由来間葉系細胞による顎骨再生療法の評価と臨床展開 (2017)
  • Author(s): 土屋周平，清水 忍，片桐 渉
  • Organizer: 第17回日本再生医療学会総会
  • Invited
• [Presentation] 骨髄由来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，若山有紀子，鶴田剛士，渡邉純奈，日比英晴
  • Organizer: 第61回日本口腔外科学会総会・学術大会
  • Place of Presentation: 幕張メッセ（千葉県幕張市）
  • Year and Date: 2016-11-25
• [Presentation] Translational research for bone regeneration by the conditioned medium from mesenchymal stem cells after maxillary sinus floor elevation (2016)
  • Author(s): Katagiri W, Watanabe J, Toyama N, Sakaguchi K, Sugimura-Wakayama-Y, Osugi M, Kojima T, Kobayashi T
  • Organizer: The 55th Congress of the Korean Association of Maxillofacial Plastic and Reconstructive Surgeons
  • Place of Presentation: 大邱市（大韓民国）
  • Year and Date: 2016-11-04
• [Presentation] 幹細胞由来培養上清を模した成長因子混合剤による新たな歯周組織再生法 (2016)
  • Author(s): 坂口晃平，片桐 渉，大杉将嗣，酒井 陽，若山有紀子，鶴田剛士，日比英晴
  • Organizer: 第37回日本炎症・再生医学会
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2016-06-16
• [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, T Kawai, Hibi H
  • Organizer: 31st Annual Scientific Meeting of Association for Osseointegration
  • Place of Presentation: サンディエゴ、アメリカ合衆国
  • Year and Date: 2016-02-17
  • Int'l Joint Research
• [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総会・学術大会
  • Place of Presentation: 名古屋国際会議場、名古屋市
  • Year and Date: 2015-10-16