Induced Adipocyte Cell-Sheet Ameliorates Cardiac Dysfunction in a Mouse Myocardial Infarction Model A Novel Drug Delivery System for Heart Failure

Background—A drug delivery system that constitutively and effectively retains cardioprotective reagents in the targeted myocardium has long been sought to treat acute myocardial infarction. We hypothesized that a scaffold-free induced adipocyte cell-sheet (iACS), transplanted on the surface of the heart, might intramyocardially secrete multiple cardioprotective factors including adiponectin (APN), consequently attenuating functional deterioration after acute myocardial infarction. Methods and Results—Induced ACS were generated from adipose tissue–derived cells of wild-type (WT) mice (C57BL/6J), which secreted abundant APN, hepatocyte growth factor, and vascular endothelial growth factor in vitro. Transplanted iACS secreted APN into the myocardium of APN-knockout (KO) mice at 4 weeks. APN was also detected in the plasma of iACS-transplanted APN-KO mice at 3 months (245±113 pg/mL). After left anterior descending artery ligation, iACS, generated from either WT (n=40) or APN-KO (n=40) mice, were grafted onto ...