Adipose Tissue-Derived Stem Cells Suppress Acute Cellular Rejection by TSG-6 and CD44 interaction in Rat Kidney Transplantation.

• Project/Area Number: 25861419
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Osaka University
• Principal Investigator: KATO Taigo 大阪大学, 医学部附属病院, 医員 (70648021)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 間葉系幹細胞 / 腎移植 / 急性拒絶反応

Outline of Final Research Achievements

In this study, we evaluated the beneficial effects of ADSCs in rat kidney transplantation and analysed the underlying molecular mechanism. DA rat kidneys were transplanted into Lewis rats. Histological findings of the ADSCs group revealed a reduced rejection grade, while the number of infiltrated CD4+/CD8+ T cells was also significantly decreased as compared to the control. Relative to these findings, injection of ADSCs led to a significantly prolonged mean graft survival compared with the control. In vitro, autologous ADSCs dose-dependently suppressed alloreactive lymphocytes. Moreover, ADSCs increased the level of tumor necrosis factor-inducible gene 6 protein (TSG-6) in MLR, which has anti-inflammatory capacity. Recombinant TSG-6 markedly suppressed alloreactive T cells through downregulating CD44, which may lead to the suppression of T cell activation and infiltration into allografts.

Research Products

• [Journal Article] Adipose Tissue-Derived Stem Cells Suppress Acute Cellular Rejection by TSG-6 and CD44 interaction in Rat Kidney Transplantation (2014)
  • Author(s): Taigo Kato, Masayoshi Okumi, Masahiro Tanemura, Koji Yazawa, Yoichi Kakuta, Kazuaki Yamanaka, Koichi Tsutahara, Yuichiro Doki, Masaki Mori, Shiro Takahara, and Norio Nonomura
  • Journal Title: Transplantation Volume: Aug 15;98(3) Issue: 3 Pages: 277-84
  • DOI: 10.1097/tp.0000000000000230
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] ラット腎移植モデルにおける脂肪組織由来間葉系幹細胞（Adipose Tissue-Derived Stem Cells）の免疫調整効果およびその作用機序についての検討 (2014)
  • Author(s): 加藤大悟、奥見雅由、山中和明、角田洋一、野々村祝夫
  • Organizer: 第23回泌尿器分子・細胞研究会
  • Place of Presentation: 山形
• [Presentation] Adipose Tissue-Derived Stem Cells Suppress Acute Cellular Rejection via TSG-6 and CD44 interaction in a Rat Kidney Transplantation (2014)
  • Author(s): Kato T, Okumi M, Kakuta Y, Yanamaka K, Takahara S, Nonomura N
  • Organizer: World Transplant Congress 2014
  • Place of Presentation: 米国・サンフランシスコ
• [Presentation] Adipose Tissue-Derived Stem Cells Suppress Acute Cellular Rejection via TSG-6 and CD44 interaction in a Rat Kidney Transplantation (2013)
  • Author(s): Kato T, Okumi M, Nonomura N
  • Organizer: The 13th Congress of the Asian Society of Transplantation
  • Place of Presentation: 京都
• [Presentation] ラット腎移植モデルにおける脂肪組織由来間葉系幹細胞（Adipose Tissue-Derived Stem Cells）の免疫調整効果についての検討
  • Author(s): 加藤大悟、奥見雅由、山中和明、角田洋一、高原史郎、野々村祝夫
  • Organizer: 第40回日本臓器保存生物医学会
  • Place of Presentation: 東京