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

利用诱导脂肪细胞片层开发靶向脂联素递送系统

• 批准号: 22659251
• 负责人: SAWA Yoshiki
• 金额: $ 2.01万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659251/
• 关键词: Drug delivery system; 劇症型心筋炎; アディポネクチン; Cell therapy

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.

我们假设基于细胞表的脂联素的递送系统可能会在大鼠的实验自身免疫性心肌炎（EAM）中诱导免疫耐受性和功能恢复。通过诱导合成性培养的脂肪组织衍生的干细胞分化到温度响应式菜肴上的脂肪细胞中，无脚手架诱导的脂肪细胞表（IAC）是通过诱导合成培养的脂肪组织衍生的干细胞而产生的。 IACS的上清液中含有高水平的脂联素和肝细胞生长因子（HGF），以及从EAM大鼠脾细胞中排序的CD4阳性T细胞的增殖减少。这种组织工程的IACS治疗通过持续向心脏供应脂肪细胞因子抑制了心脏内心内T细胞的活性和炎症，因此在EAM大鼠模型中诱导了功能恢复。这些发现支持将此策略转换为临床领域。

项目成果

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

通过移植诱导脂肪细胞片将脂肪细胞因子靶向输送至心脏，使大鼠自身免疫相关暴发性心肌炎产生免疫耐受和功能恢复

• 发表时间: 2011
• 作者: 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
• 通讯作者: 澤芳樹

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

通过移植诱导脂肪细胞片层将脂肪细胞因子靶向输送至心脏，可在大鼠自身免疫相关心肌炎中产生免疫耐受和功能恢复

• 发表时间: 2011
• 作者: Sokichi Kamata;Shigeru Miyagawa;Satsuki Fukushima;Yukiko Imanishi;Atsuhiro Saito;Norikazu Maeda;Yoshiki Sawa
• 通讯作者: Yoshiki Sawa

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

脂联素产生细胞片对心肌炎大鼠心肌再生作用的检测

• 发表时间: 2011
• 作者: Sokichi Kamata;Shigeru Miyagawa;Satsuki Fukushima;Yukiko Imanishi;Atsuhiro Saito;Norikazu Maeda;Yoshiki Sawa;菊田健一郎;鎌田創吉
• 通讯作者: 鎌田創吉