Novel approach of induction of donor specific immune tolerance: adoptive transfer of Treg cells combined with MF1 gene transfection

2013 Fiscal Year Final Research Report

• Project/Area Number: 21390446
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: Osaka Medical College
• Principal Investigator: AZUMA Haruhito 大阪医科大学, 医学部, 教授 (40231914)
• Co-Investigator(Kenkyū-buntansha): ISAKA Yoshitaka 大阪大学, 医学(系)研究科, 准教授 (00379166) ; ASAHI Michio 大阪医科大学, 医学部, 教授 (10397614) ; LI Xiaokang 国立成育医療センター(研究所), 移植, 外科研究部, 室長 (60321890) ; TAKAHARA Siro 大阪大学, 医学(系)研究科(研究院), 寄附講座教授 (70179547)
• Project Period (FY): 2009-04-01 – 2014-03-31
• Keywords: CD28-Superagonist / 非特異的免疫制御細胞 / Treg バンク / CD34+幹細胞 / ドナー特異的な免疫寛容 / MF-1遺伝子導入 / レンチウイルス / 超音波照射遺伝子導入法

Research Abstract

We have developed a novel approach of highly effective gene transfection technique using lenti-virus vector combined with ultrasound mediated gene transfection procedure. We have performed successful gene transfection of metron factor, which is the engineered chimeric factors containing selected functional domains of HGF and MSP, into the transplanted kidney tissue. Local production of MF-1, which may enhance the expansion of Treg cells in vivo, combined with .the adoptive transfer of Treg cells, successfully induced the donor specific immune tolerance in more than 70% of recipients in our rat kidney transplant model.

Research Products

• [Journal Article] Utility of the novel bladder preservation therapy, BOAI-CDDP-radiation (OMC-regimen), for elderly patients with invasive bladder cancer (2011)
  • Author(s): Azuma, H., Inamoto, T., Ibuki, N., Ubai, T., Kotake, Y., Takahara, K., Kiyama, S., Nomi, H., Uehara, H., Komura, K., Yamamoto, K., Narumi, Y., Katsuoka, Y
  • Journal Title: Int. J. Oncol Volume: 38 Pages: 13-243
• [Journal Article] Induction of Donor-Specific Tolerance Using Superagonistic CD28 Antibody in Rat Renal Allografts : Regulatory T-Cell Expansion Before Engraftment May Be Important (2010)
  • Author(s): Azuma, H., Isaka,Y., Nomi, H., Inamoto, T., Li, XK., Hőunig, T., Takabatake, Y., Ichimaru, N., Ibuki, N., Matsumoto, K., Ubai, T., Katsuoka, Y., Takahara, S.
  • Journal Title: Transplantation Volume: 90(12) Pages: 1328-1335
• [Journal Article] Utility of transrectal ultrasonography guidance and seven key elements of operative skill for early recovery of urinary continence after laparoscopic radical prostatectomy
  • Author(s): Azuma, H., Ibuki, N., Inamoto, T., Koyama, K., Utimoto, S., Fujisue, Y., Mizutani, Y., Nomi, H., Ubai, T., Katsuoka, Y
  • Journal Title: Int. J. Oncol Volume: (In press)
• [Presentation] 移植腎慢性機能不全の発症メカニズムとその治療 : 新規免疫寛容誘導法の開発に向けて (2012)
  • Author(s): 東 治人
  • Organizer: 第27回日本生殖免疫学会総会・学術集会
  • Place of Presentation: 大阪医科大学( 大阪)
  • Year and Date: 2012-12-09
• [Presentation] 免疫学的ハイリスク症例の腎移植について (2012)
  • Author(s): 平野 一, 東 治人, 八木澤 隆史, 野崎 大史, 清水 朋一, 石田 英樹, 田邊 一成
  • Organizer: 第42回日本腎臓学会西部学術大会
  • Place of Presentation: 沖縄コンベンションセンター(沖縄)
  • Year and Date: 2012-10-26