Macrophages from blood speed healing processp
Study shows strong advantages
Using macrophages prepared from a unit of blood, researchers treated pressure ulcers of 72 elderly patients and compared the results to those of conventional treatment performed on a control group of 127 patients. The conclusion: Blood-derived macrophages were significantly more effective than conventional methods for treatment of ulcers in this patient cohort.1
Statistical analysis of the results showed a significant difference both in efficacy of treatment and healing time between the two groups. Twenty-seven percent (36 out of 131) of the ulcers in the macrophage-treated group healed completely, compared with only 6% (115 out of 248) of the ulcers in the control group. No side effects were noted in the macrophage-treated group.
"Our results suggest that macrophage treatment may, at least theoretically, have certain advantages over treatment of ulcers with growth factors or cytokines. In addition to their fundamental protective functions of ingesting and killing invading organisms and their central role in immune response in presenting antigen to lymphocytes, macrophages can produce and release most, if not all, of the required growth factors and cytokines in situ," says David Danon, a researcher at Israel's Center for Biology of Aging, who led the study.
In early experiments, the investigators, located at various medical and research facilities in Israel, prepared macrophages in a tissue culture laboratory and injected them into the periphery of 10 wounds of elderly patients. The results were encouraging, particularly because the appearance of new granulation tissue was not restricted to the injected half of the periphery. But preparation of the macrophages proved costly and required a fully equipped tissue culture laboratory and a specialized technician.
Another method of preparation was sought. The answer turned out to be a closed sterile system comprising a number of interconnected plastic bags that contain donor blood and the reagents required for extracting the macrophages from a blood unit. The entire process does not require a tissue culture lab, ensures sterility, is cost-effective, and takes less than three and a half hours, according to Danon.
During the study, macrophages were injected around the entire wound periphery at 1 cm intervals. No debridement was performed before or after treatment. When possible, the ulcer was turned face up so that the rest of the macrophage suspension could be poured over its surface. For deep ulcers, the suspension was poured directly into the wound. Macrophage application was followed by a Ringers solution compress on a cotton gauze pad, which was kept moist and changed daily. Ulcers were treated with macrophages only once, except for nine ulcers in four patients for whom a second treatment was given after two months because response to the initial application seemed delayed.
Complete healing of an ulcer was defined as a positive outcome. "Only a closed, healed ulcer was considered a positive response to treatment, regardless of its original size and site, or the age, sex, health status, or medical history of the patient," says Danon. ". . . It is widely acknowledged that any conventional treatment of ulcers may be temporarily effective showing a reduction in their surface area and depth. However, such improvement is often followed by regression. For this reason we considered a positive response to treatment only an ulcer that was completely healed."
To track wound healing, photographs were taken every two weeks. Because the study did not control for randomization, Danon defines it as a nonrandomized controlled trial. A double-blind trial was ruled out because the experimental treatment was given by injection, while conventional treatment does not require injection of any substances.
The American Red Cross is interested in Danon's research and is investigating his method of isolating blood monocytes, says Steve Wagner, a scientist with the Red Cross in Rockville, MD. "We haven't defined a role for this yet, but we're exploring the use of macrophages," he says.
Reference
1. Danon D, Madjar J, Edinov E, et al. Treatment of human ulcers by application of macrophages prepared from a blood unit. Exp Gerontol 1997; 32:633-641.
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