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Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart.
- Source :
-
Circulation [Circulation] 2006 Jul 04; Vol. 114 (1 Suppl), pp. I94-100. - Publication Year :
- 2006
-
Abstract
- Background: Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium.<br />Methods and Results: Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (approximately 4 x 10(5) cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (n=8) immediately after coronary artery ligation. The control group (n=9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide-nanoparticle-labeled cells. After 5 weeks, scar vessel density (+/-SE) (25+/-4 versus 10+/-1 per mm2; P<0.05), myofibroblast accumulation, and recruitment of resident monocytes and macrophages were greater in AMS-treated hearts compared with controls. Serial echocardiography studies, before and 5 weeks after injection, showed that AMS improved scar thickening (0.15+/-0.01 versus 0.11+/-0.01 cm; P<0.05), reduced left ventricular (LV) diastolic dilatation (0.87+/-0.02 versus 0.99+/-0.04 cm; P<0.05), and improved LV fractional shortening (31+/-2 versus 20+/-4%; P<0.05), compared with controls.<br />Conclusions: Early after myocardial infarction, injection of AMS accelerates vascularization, tissue repair, and improves cardiac remodeling and function. Our work suggests a novel clinically relevant option to promote the repair of ischemic tissue.
- Subjects :
- Adolescent
Adult
Animals
Antigens, CD analysis
Antigens, Differentiation, Myelomonocytic analysis
Cicatrix pathology
Female
HLA-DR Antigens analysis
Human Growth Hormone analysis
Humans
Macrophages chemistry
Macrophages physiology
Magnetic Resonance Imaging
Male
Myocardial Infarction pathology
Neovascularization, Physiologic
Osmotic Pressure
Rats
Rats, Sprague-Dawley
Transplantation, Heterologous
Ventricular Function, Left
Wound Healing
Macrophage Activation
Macrophages transplantation
Myocardial Infarction surgery
Ventricular Remodeling
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 114
- Issue :
- 1 Suppl
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 16820652
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.105.000331