title: Induced adipocyte cell-sheet ameliorates cardiac dysfunction in a mouse myocardial infarction model: a novel drug delivery system for heart failure.
abstract: 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.
  
  
  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 the surface of the anterior left ventricular wall of WT mice, or only left anterior descending artery ligation was performed (n=43). Two days later, inflammation and infarct size were significantly diminished only in the WT-iACS treated mice. One month later, cardiomyocyte diameter and percent fibrosis were smaller, whereas ejection fraction and survival were greater in the WT-iACS treated mice compared with the KO-iACS-treated or nontreated mice.
  
  
  CONCLUSIONS
  Cardioprotective factors including APN, hepatocyte growth factor, and vascular endothelial growth factor were secreted from iACS. Transplantation of iACS onto the acute myocardial infarction heart attenuated infarct size, inflammation, and left ventricular remodeling, mediated by intramyocardially secreted APN in a constitutive manner. This method might be a novel drug delivery system to treat heart disease.
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Imanishi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Norikazu
authors.initials: N
authors.lastname: Maeda
authors.forename: Satsuki
authors.initials: S
authors.lastname: Fukushima
authors.forename: Satoru
authors.initials: S
authors.lastname: Kitagawa-Sakakida
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.forename: Ayumu
authors.initials: A
authors.lastname: Hirata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D013504:Cardiovascular Surgical Procedures; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D006321:Heart / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D052242:Adiponectin; D002316:Cardiotonic Agents; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor