Determination of Endogenous Cytokines in Chronic Wounds

Cooper, Diane M.; Yu, Erik Z.; Hennessey, Patrick J.; Ko, Francis; Robson, Martin C.

doi:10.1097/00000658-199406000-00012

Cited by 200 publications

(126 citation statements)

References 9 publications

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“…A recent study that analyzed acute human wound fluid also found predominantly PDGF-AA (12). Another study in which wound fluid from chronic pressure ulcers was analyzed found variable amounts of PDGF present, but the assay was unable to discriminate among the isoforms (49). Recently, Ansel and co-workers (47) identified PDGF-AA in provisional matrix within experimental human wounds.…”

Section: Discussionmentioning

confidence: 99%

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Pierce¹,

Tarpley²,

Tseng³

et al. 1995

J. Clin. Invest.

217

137

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Some human chronic dermal wounds treated with recombinant platelet-derived growth factor-BB (rPDGF-BB) show increased healing coupled with fibroblast activation and granulation tissue formation. To determine whether endogenous PDGF is associated with healing and nonhealing dermal ulcer phenotypes, we developed monoclonal antibodies capable of recognizing the three isoforms of PDGF, AA, AB, and BB dimers, and capable of discriminating between two alternatively spliced A chain transcripts. We detected little PDGF isoform expression in normal skin and in nonhealing dermal ulcers. In contrast, in surgically created acute wounds and chronic ulcers treated with rPDGF-BB, markedly upregulated levels of PDGF-AA (long form) were found. In both types of wounds, increased PDGF-AA was detected primarily in capillaries and fibroblasts, although in rPDGF-BB-treated chronic wounds, widespread expression of PDGF-AA was somewhat delayed. With continued treatment, the long form of PDGF-AA, which can preferentially bind extracellular matrix, was expressed only in capillaries, while fibroblasts began synthesizing the short form of PDGF-AA. Within capillaries, all endothelial cells and varying numbers of pericytes and smooth muscle cells contained PDGF-AA. In all wounds, macrophages and keratinocytes were not a major contributor. While PDGF-BB and PDGF-AB were present in a minority of healing wounds, they were usually present at lower levels than PDGF-AA. PDGF-18 receptors, which bind only PDGF-BB and not other isoforms, were found in normal skin and granulation tissue, providing a molecular basis for treating human chronic wounds with exogenous rPDGF-BB. (J. Clin.

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Section: Discussionmentioning

confidence: 99%

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Pierce¹,

Tarpley²,

Tseng³

et al. 1995

J. Clin. Invest.

217

137

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“…In preliminary experiments with defined amounts of proteins, a recovery of 88-98% was described when extracting the beads with equal volumes of phosphate buffered saline for 12 hours (Cooper et al 1994).…”

Section: Sampling Of Chronic Wound Fluidsmentioning

confidence: 99%

Wound Fluid Diagnostics in Diabetic Foot Ulcers

Löffler¹,

Schmohl²,

Schneiderhan‐Marra³

et al. 2011

Global Perspective on Diabetic Foot Ulcerations

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“…In a small study published in 1993, Lev-Ran and Hwang (11) reported an elevation of PDGF and EGF in the plasma of diabetic subjects compared with control subjects. However, Cooper et al (12) showed that a number of growth factors were markedly reduced in wound fluid from chronic wounds compared with acute wounds. Bennett and Schultz (13) postulated increased destruction or inhibition of growth factors by elevated levels of proinflammatory cytokines and metallomatrix protein following repeated trauma and infection.…”

mentioning

confidence: 99%

Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers

et al. 2003

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OBJECTIVE -To study the healing effect of recombinant human epidermal growth factor (hEGF) on diabetic foot ulcers. RESEARCH DESIGN AND METHODS-A total of 127 consecutive patients were screened and 61 diabetic subjects were recruited into this double-blind randomized controlled study. Predetermined criteria were used for diagnosis and classification of the diabetic wound. The patients were randomized into three groups. All patients attended our Diabetes Ambulatory Care Center every other week for joint consultation with the diabetologist and the podiatrist. Group 1 (control) was treated with Actovegin 5% cream (Actovegin), group 2 with Actovegin plus 0.02% (wt/wt) hEGF, and group 3 with Actovegin plus 0.04% (wt/wt) hEGF. The study end point was the complete closure of the wound. Failure to heal was arbitrarily defined as incomplete healing after 12 weeks.RESULTS -Final data were obtained from 61 patients randomly assigned into three groups. The mean ages of the patients, wound sizes, wound duration, metabolic measurements, and comorbidities were comparable within groups, except that group 3 had more female patients. Mean follow-up for the patients was 24 weeks. Data were cutoff at 12 weeks, and results were analyzed by intention to treat. After 12 weeks, in group 1 (control) eight patients had complete healing, two patients underwent toe amputation, and nine had nonhealing ulcers. In group 2 (0.02% [wt/wt] hEGF) 12 patients experienced wound healing, 2 had toe amputations, and 7 had nonhealing ulcers. Some 20 of 21 patients in group 3 (0.04% [wt/wt] hEGF) showed complete wound healing. Healing rates were 42.10, 57.14, and 95% for the control, 0.02% (wt/wt) hEGF, and 0.04% (wt/wt) hEGF groups, respectively. Kaplan-Meier survival analysis suggested that application of cream with 0.04% (wt/wt) hEGF caused more ulcers to heal by 12 weeks and increased the rate of healing compared with the other treatments (log-rank test, P ϭ 0.0003).CONCLUSIONS -Our data support the contention that application of hEGF-containing cream, in addition to good foot care from a multidisciplinary team, significantly enhances diabetic foot ulcer wound healing and reduces the healing time. Diabetes Care 26:1856 -1861, 2003D iabetic foot ulcer is a major complication of diabetes. People with diabetes show a 5-to 50-fold higher risk of nontraumatic amputation compared with individuals who do not suffer from diabetes (1). Between 1996 and 1998, diabetic patients accounted for 47% of all the lower-limb amputations performed in our hospital (M.W.T., K.-M.L., G.K., unpublished data), comparable to published data (2). The major risk factor leading to diabetic foot ulcer is poor diabetes control, which results in neuropathic and vascular changes. In general, diabetic foot ulcers are difficult to heal and frequently lead to amputation if complicated by infection and gangrene. Several new treatment modalities, such as exposure to an oxygen chamber, the use of platelet-derived growth factor (PDGF), and the application of various local dressings, have p...

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Determination of Endogenous Cytokines in Chronic Wounds

Cited by 200 publications

References 9 publications

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Wound Fluid Diagnostics in Diabetic Foot Ulcers

Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers

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