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 (Ϸ4ϫ10 5 cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (nϭ8) immediately after coronary artery ligation. The control group (nϭ9) 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.
Postoperative sternal wound infection remains a significant complication and generally causes considerable morbidity and mortality. Macrophages play a major role in the process of wound healing. In order to evaluate the efficacy of local injection of activated macrophage suspensions into open infected sternal wound space, a retrospective case-control study was conducted. Sixty-six patients with deep sternal wound infection treated by activated macrophages (group 1) and 64 patients with deep sternal wound infection treated by sternal reconstruction surgery with various regional flaps (group 2), were matched for gender, age, and risk index. In up to 54 months of follow-up of group 1, 60 patients (91%) achieved complete wound closure. Two (3%) late deaths occurred unrelated to the procedure. Mortality rate in group 2 was 29.7% (19/64). Duration of hospitalization was 22.6 days in group 1 vs. 56.2 days in group 2. Patients with deep sternal wound infection following open heart surgery that were treated by activated macrophages had significantly less mortality as well as significant reduction of hospitalization in comparison to the surgically treated group. These results illustrate the advantages of using a biologically based activated macrophage treatment.
Macrophages serve as the coordinators of the wound healing process. Since 1998 following the Israeli Ministry of health authorization, macrophage suspensions have been used for the treatment of ulcers, in more than 800 elderly and paraplegic patients suffering from decubital chronic ulcers.
As previously published, a significant number of genes showed increased levels of expression in hypo‐osmotic shock activated cells, using DNA microarrays technique. The majority of these genes are considered to be directly involved in the macrophage function and in the wound healing process.
Macrophge suspensions are prepared from a whole blood unit of healthy, young volunteer blood donors in a closed, sterile system, as previously described. The activated cells are applied to the wounds either by local injection or by direct deposition to the wound.
Between January 2000 and October 2003, 112 patients with postoperative sternal wound infection were treated with macrophage suspension. Full closure of the wounds was achieved in 104 (93%) of the patients.
Original wound surface area8–175 cm2 (mean 93)Days until treatment6–180 (mean 47)Days until 50% closure6–60 (mean 21)Days until full closure10–138 (mean 49)
No side effects were noted.
The use of macrophage suspension is a safe and effective therapeutic strategy that reduces risk of complications and morbidity and improves the quality of life for long ‐suffering patients. Length and cost of hospital stay may be reduced, as the treatment requires no hospitalization.
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