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2011 Fiscal Year Final Research Report

Analysis of engraftment kinetics of donor-derived cells in multi-cord blood transplantation

Research Project

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Project/Area Number 21591232
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

WASTANABE Nobukazu  東京大学, 医科学研究所, 特任准教授 (10334278)

Project Period (FY) 2009 – 2011
Keywords複数臍帯血移植 / 生着不全 / キメリズム解析 / HLAミスマッチ / 抗HLA抗体 / フローサイトメーター
Research Abstract

Due to its many benefits, since 2003 the number of cord blood transplantations(CBT) being performed has increased to almost equal that of bone marrow transplantation in Japan. CBT, however, can be complicated by graft failure, which must be resolved for safe transplantation. To overcome these problems, double-unit cord blood transplantation(dCBT) has been developed. In Japan, a large scale clinical trial ran from 2006 to 2010 to check the effects of dCBT on the engraftment process. The results from this and other global dCBT clinical trials, however, are controversial. Additionally, basic research are not complete. Therefore, it is very important to investigate engraftment kinetics of dCBT and develop effective protocols on the basis of research data.
At the start of this research project, we planned to analyze recipient blood after dCBT. After March 2010, however, there were no dCBT clinical trials in Japan. Therefore, we changed the project style from clinical investigation to analysi … More s of artificial chimerism samples in culture.
In 2009, we had many biotinylated commercial allele specific HLA monoclonal antibodies and we discovered red blood cell contamination in the leukocyte fraction of peripheral blood. We found that previous multi-color chimerism analysis systems could not clearly analyze different kinds of HLA-bearing white blood cells from multiple persons.
In 2010, we changed the combination of antibodies and fluorescent agents to obtain a good separation of each subpopulation and proper compensations. Finally, we successfully established an 11-color flow cytometry system for accurate analysis. We used PE-Cy5-conjugaed anti-CD235a antibody to get rid of red blood cells from gates on white blood cells for chimerism analysis. In addition, we made an anti-HLA-B62 antibody which stained cells very brightly.
In 2011, we used our 11-color flow cytometry system to analyze triple chimerism in CD4^+T cells and CD8^+T cells in a mixed lymphocyte culture to measure frequencies of three donors' white blood cells and analyze mRNA levels of each person's CD4^4 T cells and CD8^+T cells which will be useful to understand engraftment kinetics and molecular basis of allo-reactivity in future dCBT. Less

  • Research Products

    (10 results)

All 2012 2011 2010 2009 Other

All Journal Article (1 results) Presentation (8 results) Remarks (1 results)

  • [Journal Article] A rapid and efficient strategy to generate allele-specific anti-HLA monoclonal antibodies2009

    • Author(s)
      Yamazaki S, Suzuki N, Saito T, Ishii Y, Takiguchi M, Nakauchi H, Watanabe N
    • Journal Title

      J. Immunol. Method

      Volume: 343(1) Pages: 56-60

  • [Presentation] キメリズム解析/HLA-Flow法を使用したHLAミスマッチ造血細胞移植後の病態解析2012

    • Author(s)
      渡辺信和
    • Organizer
      第34回日本造血細胞移植学会、ランチョンセミナー8(日本ベクトン・ディッキンソン社)
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2012-02-24
  • [Presentation] HLA-Flow法による造血幹細胞移植後キメリズム解析への分光フローサイトメーター応用の試み2011

    • Author(s)
      渡辺信和
    • Organizer
      第40回日本免疫学会、テクニカルセミナー
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-28
  • [Presentation] 重症複合免疫不全症に対する前処置軽減臍帯血移植後の混合キメリズム病態の解析2011

    • Author(s)
      渡辺恵理、渡辺信和、森尾友宏、阿部泰子、原寿郎、中内啓光
    • Organizer
      第73回日本血液学会、口頭発表
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2011-10-15
  • [Presentation] 11カラーFACS解析による造血細胞移植後の生着動態と白血病細胞の同時モニタリング2011

    • Author(s)
      渡辺恵理、中内祐介、渡辺信和、石田宏之、中内啓光
    • Organizer
      第21回日本サイトメトリー学会、口頭発表
    • Place of Presentation
      京都市国際交流会館
    • Year and Date
      2011-06-26
  • [Presentation] Clinical diagnosis of graft failure and relapse of leukemia after HLA-mismatched hematopoietic cell transplantation by chimerism analysis using a spectral analyzer2011

    • Author(s)
      Nobukazu Watanabe, Yusuke Nakauchi, Eri Watanabe, Masaya Kakuta, Koji Futamura, Motohiro Furuki, Hiromitsu Nakauchi
    • Organizer
      CYTO2011
    • Place of Presentation
      Baltimore, MD
    • Year and Date
      2011-05-22
  • [Presentation] Rapid chimerism-switch of lymphocytes and phenotypic conversion of naive T cells early after CBT-臍帯血移植後早期のドナー由来リンパ球の生着動態2010

    • Author(s)
      山本久史、松野直史、渡辺信和、成田円、西田彩、島津浩、大田光、五十嵐夏恵、池邉太一、田結庄彩知、石綿一哉、中野伸亮、辻正徳、土橋留美子、森有紀、伊豆津宏二、内田直之、和気敦、米山彰子、牧野茂義、中内啓光、谷口修一
    • Organizer
      第72回日本血液学会
    • Place of Presentation
      横浜
    • Year and Date
      2010-09-25
  • [Presentation] Flow cytometric analysis of donor-recipient chimerism using anti-HLA antibody after HLA-mismatched hematopoietic cell and organ transplantation2010

    • Author(s)
      Stephanie C. Napier, Satoshi Yamazaki, Nobukazu Watanabe, Naofumi Matsuno, Satoshi Takahashi, Akinobu Takaki, and Hiromitsu Nakauchi
    • Organizer
      ICI 2010
    • Place of Presentation
      Kobe
    • Year and Date
      2010-08-26
  • [Presentation] Engraftment kinetics of donor-derived lymphocytes early after reduced-intensity cord blood transplantation inadults.2010

    • Author(s)
      Naofumi Matsuno, Hisashi Yamamoto, Nobukazu Watanabe, Kazuya Ishiwata, Nobuaki Nakano, Masanori Tsuji, Yuki Asano-Mori, Naoyuki Uchida, Atsushi Wake, Madoka Narita, Hiromitsu Nakauchi, Shuichi Taniguchi
    • Organizer
      The 8th Annual International Umbilical Cord Blood Transplantation Symposium
    • Place of Presentation
      Poster, San Francisco
    • Year and Date
      2010-06-05
  • [Remarks]

    • URL

      http://stemcell-u-tokyo.org/dm/

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Published: 2013-07-31  

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