TY - JOUR
T1 - Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart
AU - Leor, Jonathan
AU - Rozen, Liat
AU - Zuloff-Shani, Adi
AU - Feinberg, Micha S.
AU - Amsalem, Yoram
AU - Barbash, Israel M.
AU - Kachel, Erez
AU - Holbova, Radka
AU - Mardor, Yael
AU - Daniels, Dianne
AU - Ocherashvilli, Aharon
AU - Orenstein, Arie
AU - Danon, David
PY - 2006/7
Y1 - 2006/7
N2 - 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. 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 (≈4×10 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 mm; 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. 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.
AB - 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. 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 (≈4×10 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 mm; 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. 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.
KW - Immune system
KW - Inflammation
KW - Magnetic resonance imaging
KW - Myocardial infarction
KW - Remodeling
UR - http://www.scopus.com/inward/record.url?scp=33747154155&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.105.000331
DO - 10.1161/CIRCULATIONAHA.105.000331
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AN - SCOPUS:33747154155
SN - 0009-7322
VL - 114
SP - I94-I100
JO - Circulation
JF - Circulation
IS - SUPPL. 1
ER -