Development of new bone regeneration therapy using cytokine cocktail derived from dedifferentiated fat cells (DFAT)

• Project/Area Number: 16K20541
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Kagoshima University
• Principal Investigator: SHINOHARA Yukiya 鹿児島大学, 医歯学域歯学系, 助教 (30761647)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: DFAT / BMP-9 / 骨再生 / 歯周病 / ADSC / 脱分化脂肪細胞(DFAT)

Outline of Final Research Achievements

The purpose of this study was development of new bone regenerative therapy for lost bone tissues due to periodontal and oral disease by using de-differentiated fat cells(DFAT) culture supernatant of bone morphogenetic protein(BMP)-9 and FK506 costimulation. In vitro study demonstrated that BMP-9 and FK506 costimulation induces increase of various cytokine in rat DFAT cells culture supernatant. Furthermore , we demonstrated that rDFAT cells culture supernatant of BMP-9 and FK506 costimulation have bone regenerative potential in rat calvarial defects model.

Research Products

• [Journal Article] Development of a new model for training of initial periodontal therapy (2018)
  • Author(s): 町頭 三保、梅田 誠、野口 和行、中村 利明、白方 良典、中村 梢、迫田 賢二、瀬名 浩太郎、篠原 敬哉、橋口 千琴、田口 洋一郎
  • Journal Title: Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology) Volume: 60 Issue: 1 Pages: 44-51
  • DOI: 10.2329/perio.60.44
  • NAID: 130006594272
  • ISSN: 0385-0110, 1880-408X
  • Peer Reviewed / Open Access
• [Journal Article] Periodontal wound healing following reciprocal autologous root transplantation in class III furcation defects (2017)
  • Author(s): Takeuchi Naoshi、Shirakata Yoshinori、Shinohara Yukiya、Sena Kotaro、Noguchi Kazuyuki
  • Journal Title: Journal of Periodontal & Implant Science Volume: 47 Issue: 6 Pages: 352-352
  • DOI: 10.5051/jpis.2017.47.6.352
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of the effects of recombinant human bone morphogenetic protein-2 and -9 on bone formation in rat calvarial critical-size defects. (2017)
  • Author(s): Nakamura T, Shirakata Y, Shinohara Y, Miron RJ, Hasegawa-Nakamura K, Fujioka-Kobayashi M, Noguchi K.
  • Journal Title: Clin Oral Investig. Volume: 印刷中 Issue: 9 Pages: 2671-2679
  • DOI: 10.1007/s00784-017-2069-3
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Osteogenic potential of recombinant human bone morphogenetic protein-9/absorbable collagen sponge (rhBMP-9/ACS) in rat critical size calvarial defects. (2017)
  • Author(s): Nakamura T, Shirakata Y, Shinohara Y, Miron RJ, Furue K, Noguchi K.
  • Journal Title: Clin Oral Investig. Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effects of EMD liquid (Osteogain) on periodontal healing in class III furcation defects in monkeys. (2017)
  • Author(s): Shirakata Y, Miron RJ, Nakamura T, Sena K, Shinohara Y, Horai N, Bosshardt DD, Noguchi K, Sculean A.
  • Journal Title: J Clin Periodontol. Volume: 44（3） Issue: 3 Pages: 298-307
  • DOI: 10.1111/jcpe.12663
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects (2016)
  • Author(s): Yukiya Shinohara, Toshiaki Nakamura, Yoshinori Shirakata and Kazuyuki Noguchi
  • Journal Title: Dental Materials Journal Volume: 35 Issue: 3 Pages: 454-460
  • DOI: 10.4012/dmj.2015-242
  • NAID: 130005155194
  • ISSN: 0287-4547, 1881-1361
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Recombinant human bone morphogenetic protein-9 potently induces osteogenic differentiation of human periodontal ligament fibroblasts (2016)
  • Author(s): Sawako Fuchigami, Toshiaki Nakamura, Kirara Furue, Kotaro Sena, Yukiya Shinohara and Kazuyuki Noguchi
  • Journal Title: European Journal of Oral Science Volume: 124 Issue: 2 Pages: 151-157
  • DOI: 10.1111/eos.12249
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] A comparative study of the effects of recombinant human bone morphogenetic protein-2 and -9 on bone formation in rat calvarial critical size defects. (2017)
  • Author(s): Toshiaki Nakamura, Yoshinori Shirakata, Yukiya Shinohara, RJ Miron, Kozue Hasegawa-Nakamura
  • Organizer: Osteology Japan
  • Int'l Joint Research
• [Presentation] Healing of two-wall intrabony defects following treatment with a novel enamel matrix derivative formulation (Osteogain). A preclinical study in non-human primates. (2016)
  • Author(s): Y Shirakata, T Nakamura, RJ Miron, Y Shinohara, K Sena, K Noguchi, A Sculean
  • Organizer: 2nd International Symposium Regeneration and Esthetics in Periodontology and Implant Dentistry
  • Place of Presentation: Bern（Switzerland)
  • Year and Date: 2016-11-18
  • Int'l Joint Research
• [Presentation] サル根分岐部病変Ⅲ度に対するOsteogainと吸収性コラーゲンスポンジ を用いた歯周組織再生 (2016)
  • Author(s): 白方良典, 瀬名浩太郎, 中村利明 ,篠原敬哉, 寶来直人, 野口和行
  • Organizer: 第59回秋季日本歯周病学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県・新潟市）
  • Year and Date: 2016-10-07
• [Presentation] 歯周基本治療のための新たな教育用模型の開発 (2016)
  • Author(s): 町頭三保、中村利明、白方良典、中村梢、迫田賢二、瀬名浩太郎、篠原敬哉、橋口千琴、田口洋一郎、梅田誠、野口和行
  • Organizer: 第59回秋季日本歯周病学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県・新潟市）
  • Year and Date: 2016-10-07
• [Presentation] Regenerative effect of Osteogain in class Ⅲ furcations (2016)
  • Author(s): Y Shirakata, RJ Miron, T Nakamura, K Sena, Y Shinohara, DD Bosshardt, K Noguchi, A Sculean
  • Organizer: The 46th Annual Meeting of the Swiss Society of Periodontology
  • Place of Presentation: Bern(Switzerland)
  • Year and Date: 2016-09-01
  • Int'l Joint Research
• [Presentation] Recombinant human bone morphogenetic protein-9/コラーゲン担体がラット頭蓋骨欠損の骨形成に及ぼす影響 (2016)
  • Author(s): 篠原敬哉, 中村利明, 白方良典, 古江きらら, 野口和行
  • Organizer: 第59回春季日本歯周病学会
  • Place of Presentation: かごしま県民交流センター（鹿児島県・鹿児島市）
  • Year and Date: 2016-05-20
• [Presentation] サル2壁性骨欠損における新規エナメルマトリックスデリバテイブ(Osteogain) による歯周組織再生効果 (2016)
  • Author(s): 白方良典, 篠原敬哉, 瀬名浩太郎, 中村利明, 野口和行
  • Organizer: 平成28年度日本歯周病学会九州5大学・日本臨床歯周病学会九州支部合同研修会
  • Place of Presentation: 長崎県歯科医師会館（長崎県・長崎市）