Back to Search
Start Over
Induced adipocyte cell-sheet ameliorates cardiac dysfunction in a mouse myocardial infarction model: a novel drug delivery system for heart failure.
Induced adipocyte cell-sheet ameliorates cardiac dysfunction in a mouse myocardial infarction model: a novel drug delivery system for heart failure.
- Source :
-
Circulation [Circulation] 2011 Sep 13; Vol. 124 (11 Suppl), pp. S10-7. - Publication Year :
- 2011
-
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.<br />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 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.<br />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.
- Subjects :
- Adipocytes cytology
Adiponectin metabolism
Animals
Cardiovascular Surgical Procedures
Heart physiology
Heart Failure pathology
Heart Failure surgery
Hepatocyte Growth Factor metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Myocardial Infarction pathology
Myocardial Infarction surgery
Treatment Outcome
Vascular Endothelial Growth Factor A metabolism
Ventricular Remodeling physiology
Adipocytes metabolism
Adipocytes transplantation
Cardiotonic Agents therapeutic use
Cell- and Tissue-Based Therapy methods
Drug Delivery Systems methods
Heart Failure drug therapy
Myocardial Infarction drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 124
- Issue :
- 11 Suppl
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 21911798
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.110.009993