Investigation on the formation of immune privilege in tissue-engineered cartilage and its application on cartilage regenerative medicine

• Project/Area Number: 22791956
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: The University of Tokyo
• Principal Investigator: FUJIHARA Fujihara 東京大学, 医学(系)研究科(研究院), 特任助教 (50466744)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 再生医療 / 再生軟骨 / 免疫特権

Research Abstract

Involvement of immune privilege in the transplantation of tissue-engineered cartilage was examined in mice. FasL and TGF-βwere expressed on chondrocytes of tissue-engineered cartilage constructs two weeks after transplantation. The constructs of FasL-hypomorphic mice(gld) showed more infiltration of F4/80-positive cells with less accumulation of proteoglycan than those of wild-type mice. When gld chondrocytes were cultured with macrophage-like cell, RAW264, they showed modest cytotoxicity and less induction of apoptosis on RAW264 than those of wild-type mice, suggesting that expression of FasL on chondrocytes could modulate the viability and localization of macrophages, promoting the maturation of tissue-engineered cartilage.

Research Products

• [Journal Article] BMP-2-embedded atelocollagen scaffold for tissue-engineered cartilage cultured in the medium containing insulin and Triiodothyronine-A new protocol for 3D in vitro culture of human chondrocytes (2012)
  • Author(s): Ko EC, et al.
  • Journal Title: Tissue Eng Part C Methods Volume: (掲載確定)(in press) Issue: 5 Pages: 374-86
  • DOI: 10.1089/ten.tec.2011.0217
  • Peer Reviewed
• [Journal Article] Evaluation of the implant type tissue-engineered cartilage by scanning acoustic microscopy (2012)
  • Author(s): Tanaka Y, et al.
  • Journal Title: J Biosci Bioeng Volume: (掲載確定)(in press) Issue: 2 Pages: 252-7
  • DOI: 10.1016/j.jbiosc.2011.10.011
  • Peer Reviewed
• [Journal Article] Tissue responses against tissue-engineered cartilage consisting of chondrocytes encapsulated within nonabsorbable hydrogel (2011)
  • Author(s): Kanazawa S, et al.
  • Journal Title: J Tissue Eng Regen Med Volume: 97(2) Issue: 1 Pages: 186-92
  • DOI: 10.1002/term.458
  • Peer Reviewed
• [Journal Article] Administration of the insulin into the scaffold atelocollagen for tissue-engineered cartilage (2011)
  • Author(s): Ko EC, Fujihara Y, Ogasawara T, Asawa Y, Nishizawa S, Nagata S, Takato T, Hoshi K
  • Journal Title: J Biomed Mater Res A Volume: 97(2) Issue: 2 Pages: 186-92
  • DOI: 10.1002/jbm.a.33046
  • Peer Reviewed
• [Journal Article] Administration of the insulin into the scaffold atelocollagen for tissue engineered cartilage (2011)
  • Author(s): Ko E, et al.
  • Journal Title: J Biomed Mater Res A Volume: (in press(掲載確定))
  • Peer Reviewed
• [Journal Article] Utility of NucleoCounter for the chondrocyte count in the collagenase digest of human native cartilage (2010)
  • Author(s): Yonenaga K, Nishizawa S, Akizawa M, Asawa Y, Fujihara Y, Takato T, Hoshi K
  • Journal Title: Cytotechnology Volume: 62(6) Issue: 6 Pages: 539-45
  • DOI: 10.1007/s10616-010-9304-y
  • Peer Reviewed
• [Journal Article] The optimal conditions of chondrocyte isolation and its seeding in the preparation for cartilage tissue engineering (2010)
  • Author(s): Yonenaga K, Nishizawa S, Fujihara Y, Asawa Y, Sanshiro K, Nagata S, Takato T, Hoshi K
  • Journal Title: Tissue Eng Part C Methods Volume: 16(6) Issue: 6 Pages: 1461-9
  • DOI: 10.1089/ten.tec.2009.0597
  • Peer Reviewed
• [Journal Article] The optimization of porous polymeric scaffolds for chondrocyte/atelocollagen based tissue-engineered cartilage (2010)
  • Author(s): Tanaka Y, Yamaoka H, Nishizawa S, Nagata S, Ogasawara T, Asawa Y, Fujihara Y, Takato T, Hoshi K
  • Journal Title: Biomaterials Volume: 31(16) Issue: 16 Pages: 4506-16
  • DOI: 10.1016/j.biomaterials.2010.02.028
  • Peer Reviewed
• [Journal Article] The effects of rapid- or intermediate-acting insulin on the proliferation and differentiation of cultured chondrocytes (2010)
  • Author(s): Iwata K, Asawa Y, Fujihara Y, Tanaka Y, Nishizawa S, Nakagawa T, Nagata S, Takato T, Hoshi K
  • Journal Title: Curr Aging Sci Volume: 3 Issue: 1 Pages: 26
  • DOI: 10.2174/1874609811003010026
  • Peer Reviewed
• [Journal Article] The effects of rapid- or intermediate-acting insulin on the proliferation and differentiation of cultured chondrocytes (2010)
  • Author(s): Iwata K, et al.
  • Journal Title: Curr Aging Sci Volume: 3 Pages: 26-33
  • Peer Reviewed
• [Journal Article] The optimization of porous polymeric scaffolds for chondrocyte/atelocollagen based tissue-engineered cartilage (2010)
  • Author(s): Tanaka Y, et al.
  • Journal Title: Biomaterials Volume: 31 Pages: 4506-4516
  • Peer Reviewed
• [Journal Article] Utility of NucleoCounter for the chondrocyte count in the collagenase digest of human native cartilage (2010)
  • Author(s): Yonenaga K, et al.
  • Journal Title: Cytotechnology Volume: 62 Pages: 539-545
  • Peer Reviewed
• [Journal Article] The optimal conditions of chondrocyte isolation and its seeding in the preparation for cartilage tissue engineering (2010)
  • Author(s): Yonenaga K, et al.
  • Journal Title: Tissue Eng Part C Methods Volume: 16 Pages: 1461-1469
  • Peer Reviewed
• [Presentation] 耳介軟骨細胞におけるFas ligandの発現メカニズムの検討と再生軟骨移植への応用 (2011)
  • Author(s): 藤原夕子, ほか
  • Organizer: 第10回再生医療学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-02
• [Presentation] 再生軟骨組織における免疫特権因子の発現と機能 (2011)
  • Author(s): 藤原夕子, ほか
  • Organizer: 第七回医工連携研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-02-02
• [Presentation] Chondrocytes in tissue-engineered cartilage using scaffolds could suppress tissue reactions through formation of immune privilege (2011)
  • Author(s): Fujihara Y et al
  • Organizer: 10th World Congress on Inflammation
  • Place of Presentation: Paris France
• [Presentation] 軟骨細胞に発現するMIFは、再生軟骨組織におけるマクロファージの局在制御を介して、軟骨成熟にに貢献する (2011)
  • Author(s): 藤原夕子, ほか
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 千葉
• [Presentation] Chondrocytes in tissue-engineered cartilage using scaffolds could suppress tissue reactions through formation of immune privilege (2011)
  • Author(s): Fujihara Y, et al.
  • Organizer: 10th World Congress on Inflammation
  • Place of Presentation: Paris, France
• [Presentation] Chondrocytes could suppress the viability of macrophages, modulating tissue reactions in tissue-engineered cartilage (2010)
  • Author(s): Fujihara Y et al
  • Organizer: Regulatory Myeloid Cells
  • Place of Presentation: Virginia USA
• [Presentation] Fas ligand on chondrocytes could worsen viability of macrophages, modulating tissue reactions in tissue-engineered cartilage (2010)
  • Author(s): Fujihara Y et al
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Japan(Kobe)
• [Presentation] Chondrocytes could suppress the viability of macrophages, modulating tissue reactions in tissue-engineered cartilage (2010)
  • Author(s): Fujihara Y, et al.
  • Organizer: Regulatory Myeloid Cells
  • Place of Presentation: USA.ARLINGTON. VA
• [Presentation] Fas ligand on chondrocytes could worsen viability of macrophages, modulating tissue reactions in tissue-engineered cartilage (2010)
  • Author(s): Fujihara Y, et al.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Japan (Kobe)