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

我们推测脂联素细胞片状递送系统可能诱导实验性自身免疫性心肌炎(EAM)大鼠的免疫耐受和功能恢复。无支架诱导脂肪细胞片(IACS)是在温度反应皿上通过诱导同源培养的脂肪组织来源的干细胞分化为脂肪细胞而产生的。IACS上清液中含有高水平的脂联素和肝细胞生长因子(HGF)，并在体外抑制了从EAM大鼠脾细胞中分离出来的CD4+T细胞的增殖。这种组织工程IACS治疗通过持续向心脏提供脂肪细胞因子来抑制心肌内T细胞的活性和炎症，从而诱导EAM大鼠模型的功能恢复。这些发现支持将这一策略转化为临床领域的可能性。

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.