Development of Targeted Adiponectin Delivery System by Using Induced Adipocyte Cell-sheet

• Project/Area Number: 22659251
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: Osaka University
• Principal Investigator: SAWA Yoshiki 大阪大学, 医学系・研究科, 教授 (00243220)
• Co-Investigator(Kenkyū-buntansha): KURATANI Toru 大阪大学, 医学系・研究科, 准教授 (90448035) ; UENO Takayoshi 大阪大学, 医学系・研究科, 講師 (60437316) ; SAKAGUCHI Taichi 大阪大学, 医学系・研究科, 寄附講座准教授 (10467574) ; SHIRAKAWA Yukitoshi 大阪大学, 医学系・研究科, 助教 (20457013) ; YOSHIKAWA Yasushi 大阪大学, 医学部附属病院, 助教 (40570594) ; YAMAUCHI Takashi 大阪大学, 医学系・研究科, 助教 (20527999) ; SHIMAMURA Kazuo 大阪大学, 医学系・研究科, 寄附講座助教 (10507205) ; 宮川 繁 大阪大学, 医学系研究科, 助教 (70544237)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,140,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: Drug delivery system / 劇症型心筋炎 / アディポネクチン / Cell therapy

Research Abstract

We hypothesized that cell sheet-based delivery system of adiponectin might induce immune-tolerance and functional recovery in experimental autoimmune myocarditis(EAM) in rat. Scaffold-free induced adipocyte cell-sheet(iACS) was generated by inducing differentiation of syngeneic cultured adipose tissue-derived stem cells into the adipocytes on the temperature responsive dishes. Supernatants of iACS contained a high level of adiponectin and hepatocyte growth factor(HGF), and reduced proliferation of CD4-positive T cells that were sorted from splenocytes of the EAM rats, in-vitro. This tissue-engineered iACS treatment suppressed intramyocardial T cell activity and inflammation by persistently supplying adipocytokines to the heart, consequently inducing functional recovery in the EAM rat model. The findings support possible translation of this strategy into the clinical arena.

Research Products

• [Journal Article] Induced Adipocyte Cell-Sheet Ameliorates Cardiac Dysfunction in a Mouse Myocardial Infarction Model : A Novel Drug Delivery System for Heart Failure (2011)
  • Author(s): Yukiko Imanishi, Shigeru Miyagawa, Norikazu Maeda, Satsuki Fukushima, Satoru Kitagawa-Sakakida, Takashi Daimon, Ayumu Hirata, Tatsuya Shimizu, Teruo Okano, Iichiro Shimomura, Yoshiki Sawa
  • Journal Title: Circulation Volume: 124【suppl 1】
• [Presentation] A Targeted Delivery of Adipocytokines into the Heart by Transplantation of Induced Adipocyte Cell-Sheet Yields Immune-tolerance and Functional Recovery in Autoimmune-Associated Fulminant Myocarditis in Rat (2011)
  • Author(s): 鎌田創吉, 宮川繁, 福嶌五月, 今西悠基子, 齋藤充弘, 前田法一, 澤芳樹
  • Organizer: アメリカ心臓病学会
  • Place of Presentation: オーランド
  • Year and Date: 2011-11-14
• [Presentation] A Targeted Delivery of Adipocytokines into the Heart by Transplantation of Induced Adipocyte Cell-sheet Yields Immuno-tolerance and Functional Recovery in Autoimmune-Associated Myocarditis in Rat (2011)
  • Author(s): Sokichi Kamata, Shigeru Miyagawa, Satsuki Fukushima, , Yukiko Imanishi, Atsuhiro Saito, Norikazu Maeda, Yoshiki Sawa
  • Organizer: アメリカ心臓病学会
  • Place of Presentation: Orland, USA
  • Year and Date: 2011-11-12
• [Presentation] 心筋炎ラットに対するアディポネクチン産生細胞シートによる心筋再生効果の検討 (2011)
  • Author(s): 鎌田創吉
  • Organizer: 日本再生医療学会
  • Place of Presentation: 京王プラザホテル(東京)
• [Presentation] Induced Adipocyte Cell-Sheet Ameliorates Cardiac Dysfunction in a Mouse Myocardial Infarction Model : A Novel Drug Delivery System for Heart Failure (2010)
  • Author(s): Yukiko Imanishi, Shigeru Miyagawa, Norikazu Maeda, Satsuki Fukushima, Satoru Kitagawa-Sakakida, Takashi Daimon, Ayumu Hirata, Tatsuya Shimizu, Teruo Okano, Iichiro Shimomura, Yoshiki Sawa
  • Organizer: アメリカ心臓病学会
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-13