Induction of tolerance by rejuvenation of thymus in preclinical large animal model.

• Project/Area Number: 26293292
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Nobori Shuji 京都府立医科大学, 医学(系)研究科(研究院), 講師 (30433288)
• Co-Investigator(Kenkyū-buntansha): 山田 和彦 鹿児島大学, 医用ミニブタ・先端医療開発研究センター 臓器置換・異種移植外科分野, 教授 (40241103) ; 佐原 寿史 鹿児島大学, 医用ミニブタ・先端医療開発研究センター 臓器置換・異種移植外科分野, 准教授 (90452333)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 移植・再生 / 前臨床研究 / 免疫寛容 / 胸腺 / ミニブタ / 移植・再生医療 / トランスレーショナルリサーチ

Outline of Final Research Achievements

Our previous study suggested that rejuvenation of thymus and bone marrow from juvenile donors have important role of inducing transplant tolerance. Expression of IGF1R in thymus can be the marker of transplant tolerance. However, the important question remained whether aged, involuted thymus could also induce tolerance. We tested the IGF level in aged swine thymus after transplantation of aged thymus from aged donor. It showed rejection in aged thymus and sensitization against the donor.

Research Products

• [Journal Article] Abrogation of renal allograft tolerance in MGH miniature swine: The role of intra-graft and peripheral factors in long-term tolerance. (2014)
  • Author(s): Scalea JR, Okumi M, Villani V, Shimizu A, Nishimura H, Gillon BC, Torabi R, Cormack T, Moran S, LeGuern C, Sachs DH, Yamada K.
  • Journal Title: Am J Transplant Volume: 14 (9) Issue: 9 Pages: 2001-2010
  • DOI: 10.1111/ajt.12816
  • Peer Reviewed
• [Presentation] シンポジウム2「実験用ブタ施設の現状と今後の動向」高度前臨床移植実験：医用ミニブタを用いた大動物実験として果たすべき役割と課題 (2015)
  • Author(s): 山田和彦
  • Organizer: 第3回日本先進医工学ブタ研究会
  • Place of Presentation: 東京都
  • Year and Date: 2015-10-16
• [Presentation] Thymic transplantation to determine mechanisms of thymic involution: Insulin-like growth factor 1 receptor and forkhead box protein N1 in the thymus play a role in maintaining the juvenile thymus. (2015)
  • Author(s): ekijima M, Tasaki M, Sahara H, Shimizu A, Yamada K
  • Organizer: The 14th Congress of the Asian Society of Transplantation
  • Place of Presentation: Singapore
  • Year and Date: 2015-08-23
  • Int'l Joint Research
• [Presentation] クラウンミニブタの医用ミニブタとしての有用性 (2015)
  • Author(s): 山田和彦
  • Organizer: 第3回公開シンポジウム先進医用ミニブタの開発と前臨床研究拠点形成 プロジェクト
  • Place of Presentation: 鹿児島大学（鹿児島市）
  • Year and Date: 2015-03-24
  • Invited
• [Presentation] パネルディスカッション「ブタを用いたイノベーティブな用途研究」．ミニブタを用いた前臨床研究推進のための研究・教育拠点形成プロジェクト (2014)
  • Author(s): 山田和彦
  • Organizer: 第2回日本先進医工学ブタ研究会
  • Place of Presentation: 東レ総合研修センター（静岡県三島市）
  • Year and Date: 2014-10-24 – 2014-10-25
  • Invited