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

Jonathan Leor, Liat Rozen, Adi Zuloff-Shani, Micha S. Feinberg, Yoram Amsalem, Israel M. Barbash, Erez Kachel, Radka Holbova, Yael Mardor, Dianne Daniels, Aharon Ocherashvilli, Arie Orenstein, David Danon

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

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. 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.

Original languageEnglish
Pages (from-to)I94-I100
JournalCirculation
Volume114
Issue numberSUPPL. 1
DOIs
StatePublished - 4 Jul 2006
Externally publishedYes

Keywords

  • Immune system
  • Inflammation
  • Magnetic resonance imaging
  • Myocardial infarction
  • Remodeling

Fingerprint

Dive into the research topics of 'Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart'. Together they form a unique fingerprint.

Cite this