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To establish the next generation method for immune cell therapy in transplantation

Research Project

Project/Area Number 23390315
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionNational Research Institute for Child Health and Development

Principal Investigator

LI Xiao-Kang  独立行政法人国立成育医療研究センター, 移植免疫研究室, 室長 (60321890)

Co-Investigator(Kenkyū-buntansha) KIMURA Hiromitsu  国立成育医療研究センター, 共同研究管理室, 室長 (80115477)
TAKAHARA Shiro  大阪大学, 先端移植基盤医療学, 教授 (70179547)
OKUMI Masayoshi  大阪大学, 泌尿器学, 助教 (60512978)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2011: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Keywords移植・再生医療 / 幹細胞 / 細胞・組織
Outline of Final Research Achievements

During the study period, 1st, we established a method on differentiation DC from murine iPS cells for immune cell therapy. Also, we attempted to generate and characterize DCregs, revealed immune responsiveness regulation effects both in vitro and in vivo, and the ability to generate regulatory T-cells in vitro; 2nd, using mouse tolerant liver transplantation model, we confirmed the presence of MDSC in the grafts, significantly suppressed the T cells proliferation; 3rd, we developed a novel siRNA delivery system, specifically silencing CD40 genes, revealed the effect of the transplanted heart survival prolongation by suppressing the activation of the CD40/CD154 pathway and increased the DCreg cells; Last, we demonstrated that 5-ALA/SFC could inhibited T cell proliferation in response to alloantigens and increased number of regulatory DC and T cells, resulting in permanent cardiac allograft acceptance in mice. These findings highlight the important roles of HO-1 in inducing tolerance.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (23 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (11 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Permanent acceptance of mouse cardiac allografts with CD40 siRNA to induce regulatory myeloid cells by use of a novel polysaccharide siRNA delivery system2015

    • Author(s)
      Zhang Q, Ichimaru N, Higuchi S, Cai SJ, Hou JG, Fujino M, Nonomura N, Kobayashi M, Ando H, Uno A, Sakurai K, Mochizuki S, Adachi Y, Ohno N, Zou HJ, Xu JH, Li Xiao K*. Takahara S
    • Journal Title

      Gene Ther

      Volume: 22(3) Issue: 3 Pages: 1-10

    • DOI

      10.1038/gt.2014.119

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 5-aminolaevulinic acid with ferrous iron induces permanent cardiac allograft acceptance in mice via the induction of regulatory cells2015

    • Author(s)
      Hou JG, Zhang Q, Fujino M, Cai SJ, Ito H, Takahashi K, Abe F, Nakajima M, Tanaka T, Xu JH, Zou HJ, Ding Q, Li Xiao K*
    • Journal Title

      J Heart Lung Transplant

      Volume: 34(2) Issue: 2 Pages: 254-63

    • DOI

      10.1016/j.healun.2014.09.037

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Identification of microRNAs involved in acute rejection and spontaneous tolerance in murine hepatic allografts2014

    • Author(s)
      Morita M, Chen J, Fujino M, Kitazawa Y, Sugioka A, Zhong L, Li Xiao K*.
    • Journal Title

      Sci Rep

      Volume: 4 Issue: 1 Pages: 6649-6649

    • DOI

      10.1038/srep06649

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 5-aminolevulinic acid combined with ferrous iron enhance the expression of heme oxygenase-12014

    • Author(s)
      Nishio Y, et al.
    • Journal Title

      Int Immunopharmacol

      Volume: 19(2) Issue: 2 Pages: 300-307

    • DOI

      10.1016/j.intimp.2014.02.003

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation and characterization of regulatory dendritic cells derived from murine induced pluripotent stem cells2014

    • Author(s)
      Zhang Q, et al.
    • Journal Title

      Sci Rep

      Volume: 4 Issue: 1 Pages: 3979-3979

    • DOI

      10.1038/srep03979

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of STAT3 in regulatory T lymphocyte plasticity during acute graft-vs-host-disease2013

    • Author(s)
      Fujino M, Li Xiao K
    • Journal Title

      JAKSTAT

      Volume: 2(4) Issue: 4 Pages: e24529-e24529

    • DOI

      10.4161/jkst.24529

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-myeloablative conditioning is sufficient to induce mixed chimerism and subsequent acceptance of donor specific cardiac and skin grafts2013

    • Author(s)
      Liu C
    • Journal Title

      Int Immunopharmacol

      Volume: 未定

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow derived conventional, but not cloned, mesenchymal stem cells suppress lymphocyte proliferation and prevent graft-versus-host disease in rats2012

    • Author(s)
      Kitazawa Y
    • Journal Title

      Cell Transplant

      Volume: 21 Pages: 581-90

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a novel biomarker gene set with sensitivity and specificity to distinguish between allograft rejection and tolerance2012

    • Author(s)
      Xie L, et al
    • Journal Title

      Liver Transplant

      Volume: 18 Pages: 444-454

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion of CD98hc in T cells results in cardiac allograft acceptance by increasing regulatory T cells

    • Author(s)
      Liu Z, et al
    • Journal Title

      Transplantation

      Volume: (掲載決定)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow derived conventional, but not cloned, mesenchymal stem cells suppress lymphocyte proliferation and prevent graft-versus-host disease in rats

    • Author(s)
      Kitazawa Y, et al
    • Journal Title

      Cell Transplant

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
  • [Presentation] 5-ALA attenuate immune responses via induction of HO-1 to induce T cell and regulatory dendritic cells2014

    • Author(s)
      Li Xiao K
    • Organizer
      The 12th China Congress, International Society of Heart Research
    • Place of Presentation
      Harbin, China
    • Year and Date
      2014-08-14 – 2014-08-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] A novel preservation solution prolonged cold storage in mouse cardiac grafts2014

    • Author(s)
      Songjie Cai, Naotsugu Ichimaru, Mingyi Zhao, Li Xiao K
    • Organizer
      World Transplant Congress 2014
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-07-26 – 2014-07-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] 5-アミノレブリン酸と鉄イオンによるヘム合成の促進とヘムオキシゲナーゼ-1の誘導2014

    • Author(s)
      西尾佳明、藤野真之、趙明一、李小康
    • Organizer
      第4回ポリフィリン・ALA学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2014-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Silencing CD40 gene to induce transplantation tolerance using a novel siRNA delivery system2013

    • Author(s)
      Songjie Cai, Naotsugu Ichimaru, Sadaharu Higuchi, Masakazu Kobayashi, Atsushi Uno, Hironori Ando, Kazuo Sakurai, Yoshiyuki Adachi, Naohito Ohno, Xiao-Kang Li, Shiro Takahara
    • Organizer
      13th TTS Basic Science Symposium
    • Place of Presentation
      Paris
    • Related Report
      2013 Annual Research Report
  • [Presentation] 5-aminolevulinic acid prevents skin and internal organs inflammation and fibrosis in murine sclerodermatous grafts-versus-host disease, a model for human scleroderma2013

    • Author(s)
      Chi Liu, Xue Yang, Masayuki Fujino, Hidenori Ito, Kiwamu Takahashi, Fuminori Abe, Motowo Nakajima, Tohru Tanaka, Yoshitaka Isaka, Hiromi Rakugi, Hejian Zou, Xiao-Kang Li
    • Organizer
      Autoimmunity Congress Asia 2013
    • Place of Presentation
      Hong Kong
    • Related Report
      2013 Annual Research Report
  • [Presentation] Silencing CD40 gene to induce specific regulatory dendritic cells resulting in permanent acceptance of mouse cardiac allograft using a novel siRNA delivery system2013

    • Author(s)
      CAI Songjie, ICHIMARU Naotsugu, HIGUCHI Sadaharu, KOBAYASHI Masakazu, UNO Atsushi, Ando Hironori, ADACHI Yoshiyuki, OHNO Naohito, LI Xiaokang.
    • Organizer
      第42回日本免疫学総会
    • Place of Presentation
      幕張
    • Related Report
      2013 Annual Research Report
  • [Presentation] A novel siRNA delivery system specifically silencing target gene to induce permanent acceptance of mouse cardiac allograft2012

    • Author(s)
      Zhang Q
    • Organizer
      24th International Congress of the Transplantation Society
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] マウス肝移植モデルを用いた免疫寛容機序の解明2012

    • Author(s)
      李小康
    • Organizer
      第48回日本移植学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report
  • [Presentation] The requirement of the myeloid-derived suppressor cells for spontaneous acceptance after liver transplantation in mice2011

    • Author(s)
      Cai SJ, et al
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      幕張
    • Related Report
      2011 Annual Research Report
  • [Presentation] Long-term acceptance of cardiac allografts with superagonistanti-CD28 and anti-GITR mAbs2011

    • Author(s)
      Hou JG, et al
    • Organizer
      第40回日本免疫学会総会
    • Place of Presentation
      幕張
    • Related Report
      2011 Annual Research Report
  • [Presentation] 5-アミノレブリン酸によるヘムオキシゲナーゼ-1誘導の促進

    • Author(s)
      西尾佳明,伊東秀典,安部史紀,石塚昌宏,長原礼宗,李小康
    • Organizer
      第3回ポルフィリン-ALA学会年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 免疫抑制siRNA/多糖 複合体2012

    • Inventor(s)
      梨井康、高原史郎、櫻井和朗、小林正和、安藤弘法、樋口貞春
    • Industrial Property Rights Holder
      NapaJen Pharma, Inc
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-07-13
    • Related Report
      2012 Annual Research Report
    • Overseas

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Published: 2011-04-06   Modified: 2019-07-29  

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