Maintenance of undifferentiated state of mesenchymal stem cells using amino acids for the regulation of stem cell aging

• Project/Area Number: 15K15708
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Okayama University
• Principal Investigator: Kuboki Takuo 岡山大学, 医歯薬学総合研究科, 教授 (00225195)
• Co-Investigator(Kenkyū-buntansha): 大野 充昭 岡山大学, 医歯薬学総合研究科, 助教 (60613156) ; 前川 賢治 岡山大学, 医歯薬学総合研究科, 准教授 (20304313) ; 秋山 謙太郎 岡山大学, 大学病院, 講師 (70423291) ; 大島 正充 岡山大学, 医歯薬学総合研究科, 助教 (00548307)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アミノ酸 / 骨髄由来間葉系幹細胞 / アンチエイジング / 幹細胞 / 骨粗鬆症 / 創傷治癒

Outline of Final Research Achievements

Amino acids are essential for life and cell metabolism. We hypothesized that amino acids can regulate the stem cell phenotype and we performed a screening and found tryptophan as stemness regulator of BMSCs. Indeed, migration and colony forming ability of BMSCs was enhanced by tryptophan treatment. In vivo mice bone defect model, Tryptophan accelerated bone healing, and increased bone volume and trabecular number compared to PBS-injected group. In summary, L-tryptophan enhances the stemness and osteoblastic differentiation of BMSCs, and may be used as an essential factor to accelerate bone healing and/or prevent bone loss, such as in the case of ageing and osteoporosis.

Research Products

• [Journal Article] Cellular reprogramming using defined factors and microRNAs. (2016)
  • Author(s): Eguchi T, Kuboki T.
  • Journal Title: Stem Cells International Volume: 2016 Issue: 1 Pages: 7530942-7530942
  • DOI: 10.1155/2016/7530942
  • NAID: 120006489932
  • Peer Reviewed / Open Access
• [Journal Article] 間葉系幹細胞の新しい機能－免疫調節細胞としての間葉系幹細胞－. (2016)
  • Author(s): 秋山謙太郎，古味佳子，窪木拓男.
  • Journal Title: 日本補綴歯科学会誌 Volume: 8(4) Pages: 346-353
  • NAID: 130005279570
• [Presentation] 必須アミノ酸トリプトファンは骨形成を促進する. (2016)
  • Author(s): Pham HT，大野充昭，Hara ES，Nguyen HT，吉岡裕也，笈田育尚，秋山謙太郎，大橋俊孝，窪木拓男.
  • Organizer: ブレインストーミング2016 atカリヨンハウスin瀬戸内市
  • Place of Presentation: 瀬戸内, 日本
  • Year and Date: 2016-09-21
• [Presentation] 必須アミノ酸トリプトファンが骨代謝に与える影響. (2016)
  • Author(s): Pham HT，大野充昭，Hara ES，Nguyen HT，吉岡裕也，笈田育尚，秋山謙太郎，大橋俊孝，窪木拓男.
  • Organizer: 第2回日本骨免疫学会.
  • Place of Presentation: 沖縄, 日本
  • Year and Date: 2016-07-06
• [Presentation] Tryptophan Enhances Stemness and Osteogenesis of Bone Marrow Stromal Cells (2015)
  • Author(s): Pham HT, Ono M, Hara ES, Oida Y, Nguyen HT, Akiyama K, Kuboki T.
  • Organizer: 第63回国際歯科研究学会 日本支部学術大会
  • Place of Presentation: 福岡，日本
  • Year and Date: 2015-10-30
• [Presentation] Effect of Tryptophan to bone marrow-derived mesenchymal stromal cells on the stemness and osteogenesis in vitro and in vivo (2015)
  • Author(s): Pham HT, Ono M, Hara ES, Oida Y, Nguyen HT, Akiyama K, Kuboki T.
  • Organizer: American Society for Bone and Mineral Research
  • Place of Presentation: Seattle, USA
  • Year and Date: 2015-10-12
  • Int'l Joint Research
• [Presentation] Tryptophan enhances the stem cell phenotype and osteoblastic differentiation of bone marrow-derived mesenchymal stromal cells in vitro and in vivo (2015)
  • Author(s): Pham HT, Ono M, Hara ES, Oida Y, Nguyen HT, Akiyama K, Kuboki T.
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 東京，日本
  • Year and Date: 2015-07-23