Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart

• Published in: Circulation (New York, N.Y.) N.Y.), 2006-07, Vol.114 (1), p.I94-94-I-100
• Main Authors: LEOR, Jonathan, ROZEN, Liat, OCHERASHVILLI, Aharon, ORENSTEIN, Arie, DANON, David, ZULOFF-SHANI, Adi, FEINBERG, Micha S, AMSALEM, Yoram, BARBASH, Israel M, KACHEL, Erez, HOLBOVA, Radka, MARDOR, Yael, DANIELS, Dianne
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Animals; Antigens, CD - analysis; Antigens, Differentiation, Myelomonocytic - analysis; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Cicatrix - pathology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug toxicity and drugs side effects treatment; Female; HLA-DR Antigens - analysis; Human Growth Hormone - analysis; Humans; Investigative techniques of hemodynamics; Investigative techniques, diagnostic techniques (general aspects); Macrophage Activation; Macrophages - chemistry; Macrophages - physiology; Macrophages - transplantation; Magnetic Resonance Imaging; Male; Medical sciences; Myocardial Infarction - pathology; Myocardial Infarction - surgery; Neovascularization, Physiologic; Osmotic Pressure; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Toxicity: cardiovascular system; Transplantation, Heterologous; Ventricular Function, Left; Ventricular Remodeling; Wound Healing
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.105.000331

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. 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