Spiekstra Sander W, Breetveld Melanie, Rustemeyer Thomas, Scheper Rik J, Gibbs Susan
Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
Wound Repair Regen. 2007 Sep-Oct;15(5):708-17. doi: 10.1111/j.1524-475X.2007.00280.x.
Full-skin substitutes, epidermal substitutes, and dermal substitutes are currently being used to heal deep burns and chronic ulcers. In this study, we investigated which wound-healing mediators are released from these constructs and whether keratinocyte-fibroblast interactions are involved. Autologous skin substitutes were constructed from human keratinocytes, fibroblasts, and acellular donor dermis. Full-thickness skin was used to represent an autograft. Secretion of wound-healing mediators was investigated by means of protein array, enzyme-linked immunosorbent assay, neutralizing antibodies, and conditioned culture supernatants. Full-skin substitutes and autografts produce high amounts of inflammatory/angiogenic mediators (IL-6, CCL2, CXCL1, CXCL8, and sST2). Epidermal and dermal substitutes produced less of these proteins. Epidermal-derived proinflammatory cytokines interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) were found to mediate synergistically the secretion of these wound-healing mediators (with the exception of sST2) from fibroblasts in dermal substitutes. The secretion of proinflammatory cytokines (IL-1alpha, TNF-alpha), chemokine/mitogen (CCL5) and angiogenic factor (vascular endothelial growth factor) by epidermal substitutes and tissue remodeling factors (tissue inhibitor of metalloproteinase-2, hepatocyte growth factor) by dermal substitutes was not influenced by keratinocyte-fibroblast interactions. The full-skin substitute has a greater potential to stimulate wound healing than epidermal or dermal substitutes. Both epidermal-derived IL-1alpha and TNF-alpha are required to trigger the release of dermal-derived inflammatory/angiogenic mediators from skin substitutes.
全层皮肤替代物、表皮替代物和真皮替代物目前正用于治疗深度烧伤和慢性溃疡。在本研究中，我们调查了这些构建物释放哪些伤口愈合介质，以及是否涉及角质形成细胞与成纤维细胞的相互作用。自体皮肤替代物由人角质形成细胞、成纤维细胞和无细胞供体真皮构建而成。全层皮肤用于代表自体移植皮肤。通过蛋白质阵列、酶联免疫吸附测定、中和抗体和条件培养上清液研究伤口愈合介质的分泌情况。全层皮肤替代物和自体移植皮肤产生大量炎症/血管生成介质（IL-6、CCL2、CXCL1、CXCL8和sST2）。表皮和真皮替代物产生的这些蛋白质较少。发现表皮来源的促炎细胞因子白细胞介素-1α（IL-1α）和肿瘤坏死因子-α（TNF-α）协同介导真皮替代物中成纤维细胞分泌这些伤口愈合介质（sST2除外）。表皮替代物分泌促炎细胞因子（IL-1α、TNF-α）、趋化因子/促分裂原（CCL5）和血管生成因子（血管内皮生长因子），真皮替代物分泌组织重塑因子（金属蛋白酶组织抑制剂-2、肝细胞生长因子）不受角质形成细胞与成纤维细胞相互作用的影响。全层皮肤替代物比表皮或真皮替代物具有更大的刺激伤口愈合的潜力。表皮来源的IL-1α和TNF-α都需要触发皮肤替代物中真皮来源的炎症/血管生成介质的释放。
