Investigation on phenotypes of macrophages in transplantation of engineered tissues and its application to regenerative medicine

• Project/Area Number: 24592981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: The University of Tokyo
• Principal Investigator: YUKO FUJIHARA 東京大学, 医学(系)研究科(研究院), 特任助教 (50466744)
• Co-Investigator(Kenkyū-buntansha): HOSHI Kazuto 東京大学, 医学部附属病院, 准教授 (30344451) ; MORI Yoshiyuki 自治医科大学, 医学部, 教授 (70251296)
• Co-Investigator(Renkei-kenkyūsha): TAKATO Tsuyoshi 東京大学, 医学部附属病院, 教授 (90171454)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 再生医療 / 軟骨再生 / 組織反応 / 軟骨再生医療

Outline of Final Research Achievements

In this study, we investigated the properties of macrophages in transplantation of tissue-engineered cartilage. As to methods, human auricular chondrocytes were cultured and embedded in polylactic acid scaffold, and then transplanted subcutaneously in BALB/c-nu/nu mice. Immunohitochemical localization of F4/80-positive cells was increased by 2 weeks. Meanwhile, M1-prone macrophages were dominant in the early-stage of transplantation up to around 2 weeks, and then M2-prone macrophages surpassed them after that. Furthermore, suppressing macrophages with clodronate liposome immediate after transplantation increased the accumulation of sGAG at eight weeks. It was therefore suggested that suppression of early-stage macrophages, which were considered to be M1-prone, could be advantageous for cartilage regeneration.

Research Products

• [Journal Article] Preclinical and clinical research on bone and cartilage regenerative medicine in oral and maxillofacial region (2014)
  • Author(s): Takato T, Mori Y, Fujihara Y, Asawa Y, Nishizawa S, Kanazawa S, Ogasawara T, Saijo T, Abe T, Abe M, Suenaga H, Kanno Y, Sugiyama S, Hoshi K
  • Journal Title: Oral Sci Int Volume: 11 Pages: 45-51
  • Peer Reviewed
• [Journal Article] Macrophage-inducing fasl on chondrocytes forms immune privilege in cartilage tissue engineering, enhancing in vivo regeneration (2014)
  • Author(s): Fujihara Y, Takato T, Hoshi K, Fujihara Y, Takato T, Hoshi K
  • Journal Title: Stem Cells Volume: 印刷中 Issue: 5 Pages: 1208-19
  • DOI: 10.1002/stem.1636
  • Peer Reviewed / Open Access
• [Presentation] マクロファージのサブクラスが軟骨再生に与える影響 (2014)
  • Author(s): 藤原夕子，高戸毅，星和人
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館，沖縄
  • Year and Date: 2014-07-01 – 2014-07-04
• [Presentation] 再生軟骨移植における組織反応抑制メカニズムの解析とその臨床応用 (2013)
  • Author(s): 藤原夕子、星和人、高戸毅
  • Organizer: 第67回日本口腔科学会学術集会
  • Place of Presentation: 栃木県総合文化センター
• [Presentation] Macrophage-inducing FasL on chondrocytes forms immune privilege in cartilage tissue engineering, enhancing in vivo regeneration (2013)
  • Author(s): Fujihara Y, Takato T, Hoshi K
  • Organizer: Frontiers 2013 EPFL Symposium
  • Place of Presentation: École Polytechnique Fédérale de Lausanne, EPF Lausanne, EPFL, Lausanne, Switzerland
• [Presentation] Phenotypes of macrophages in transplantation of tissue-engineered cartilage. (2013)
  • Author(s): Fujihara Y, Hoshi K.
  • Organizer: 第42回日本免疫学会総会
  • Place of Presentation: 幕張メッセ
• [Presentation] 再生軟骨移植におけるマクロファージサブクラスの検討 (2013)
  • Author(s): 藤原夕子、高戸毅、星和人
  • Organizer: 第12回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜