Effect of Stem Cells derived from Human Exfoliated Decidious Teeth in animal model of acute liver failure-correlation between inflammation and regeneration in liver

• Project/Area Number: 15K08996
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya University
• Principal Investigator: ISHIGAMI MASATOSHI 名古屋大学, 医学部附属病院, 講師 (90378042)
• Co-Investigator(Kenkyū-buntansha): 後藤 秀実 名古屋大学, 医学系研究科, 教授 (10215501) ; 山本 朗仁 徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (50244083)
• Research Collaborator: ITO Takanori 名古屋大学, 大学院医学系研究科, 大学院生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 急性肝不全 / 歯髄由来幹細胞 / MCP-1 / sSiglec-9 / マクロファージ / 炎症 / 肝再生 / 炎症抑制

Outline of Final Research Achievements

In acute liver failure, liver regeneration is essential to be cured, however, there are no effective drugs to use for the intervention to the liver regeneration in clinical practice.
We investigated the culture medium of stem cells derived from human exfoliated dedicious teeth (SHED-CM) in animal model of acute liver failure, and showed higher efficacy compared with other stem cells. And as the abundant humoral factors in SHED-CM, we found MCP-1, which is well-known chemoattractant of monocytes-macrophages, and secreted domain of Siglec-9, which is the key factors for transition of pro- to antiinflammatory phase of macrophages, and we also found high efficacy of these two factors for improving survival of animals, supression of the inflammation, and promotion of the hepatocyte regeneration.
These two factors might become hopeful tools for the newly developement of the drugs for acute liver failure.

Research Products

• [Journal Article] Secreted ectodomain of SIGLEC-9 and MCP-1 synergistically improve acute liver failure in rats by altering macrophage polarity (2017)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Multifaceted therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for acute liver failure in rats. (2015)
  • Author(s): Matsushita Y, Ishigami M, Matsubara K, Kondo M, Wakayama H, Goto H, Ueda M, Yamamoto A
  • Journal Title: J Tissue Eng Regen Med Volume: 2015
  • Peer Reviewed / Open Access
• [Presentation] 歯髄幹細胞無血清培養上清による難治性肝疾患での有用性の検討 急性・慢性肝炎動物モデルにおける効果発現メカニズムの違いに着目して (2017)
  • Author(s): 伊藤 隆徳, 田中 卓, 山本 健太, 安藤 祐資, 安田 諭, 野村 彩, 加藤 幸一郎, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 廣岡 芳樹, 石川 哲也, 後藤 秀実
  • Organizer: 第53回日本肝臓学会総会
• [Presentation] Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 identified from dental pulp stem cells synergistically resolve acute liver failure in rats by altering macrophage polarity. (2016)
  • Author(s): Ito T, Yamamoto A, Ishizu Y, Kuzuya T, Honda T, Ishikawa T , Ishigami M, Hirooka Y, Goto H.
  • Organizer: AASLD2016
  • Place of Presentation: ボストン(米国)
  • Int'l Joint Research
• [Presentation] 新規M2マクロファージ誘導因子を用いた難治性肝疾患治療法の開発 (2016)
  • Author(s): 伊藤 隆徳, 山本 朗仁, 山本 健太, 安藤 祐資, 安田 諭, 野村 彩, 加藤 幸一郎, 新家 卓郎, 石津 洋二, 葛谷 貞二, 本多 隆, 林 和彦, 石上 雅敏, 廣岡 芳樹, 石川 哲也, 日比 英晴, 後藤 秀実
  • Organizer: JDDW2016
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)