Clinical efficacy and mechanism of bilayered living human skin equivalent (HSE) in treatment of diabetic foot ulcers.
Clinical efficacy and mechanism of bilayered living human skin equivalent (HSE) in treatment of diabetic foot ulcers.
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发表时间：
2003
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通讯作者：
H. Brem;J. Young;M. Tomic-Canic;C. Isaacs;H. Ehrlich
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作者：
H. Brem;J. Young;M. Tomic-Canic;C. Isaacs;H. Ehrlich
未标记的双层活体人皮肤等效物（HSE）由位于成纤维细胞填充的胶原网格表面的培养角质形成细胞组成。尽管HSE被FDA批准用于治疗糖尿病足和静脉淤滞性溃疡，但其临床疗效仍然有限，因为其治疗作用的分子机制尚未完全了解。因此，它经常被错误地用作皮肤移植。在这份报告中，我们描述了HSE生物学效应的机制，以及随后在加速糖尿病足溃疡愈合方面的最佳临床应用。实验将HSE移植到裸鼠身上，通过逆转录-聚合酶链反应（RT-PCR）和免疫化学方法评估各种生长因子的释放。临床：将HSE移植到11名患有糖尿病的连续患者上，这些患者具有13个非缺血性足部溃疡，并且愈合被测量为100%闭合的时间（例如，无引流和100%上皮化）。实验HSE细胞组分被确定为表达已知促进伤口愈合的15种不同的生长因子/细胞因子基因。来自裸鼠的组织学证据表明，HSE的胶原成分在移植的前七天内经历了重塑。临床：所有糖尿病足溃疡愈合时间为31.8 ± 12.4天。HSE角质形成细胞和成纤维细胞成分表达的15种生长因子的独特组合的局部释放产生糖尿病足溃疡的闭合。HSE应在与皮肤移植相同的手术条件下应用（即，无蜂窝组织炎、无引流和可忽略的细菌）。我们假设双层HSE通过特定组合和浓度的多种生长因子的局部合成和释放产生其作用，从而改善慢性伤口受损的修复过程。
UNLABELLED Bilayered living human skin equivalent (HSE) consists of cultured keratinocytes residing on the surface of a fibroblast-populated collagen lattice. Although HSE is FDA-approved for treatment of diabetic foot and venous stasis ulcers, its clinical efficacy remains limited, because the molecular mechanisms underlying its therapeutic effect are not fully understood. It is, therefore, often applied mistakenly as a skin graft. In this report, we delineate a mechanism of HSE biological effect and consequent optimal clinical use in accelerating closure of diabetic foot ulcers. EXPERIMENTAL HSE was grafted onto nude mice and the release of various growth factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Clinical: HSE was grafted onto 11 consecutive patients with diabetes who had 13 non-ischemic foot ulcers and healing was measured as time to 100% closure (e.g., no drainage and 100% epithelialized). EXPERIMENTAL HSE cellular components were determined to express 15 different growth factors/cytokine genes known to promote wound healing. Histological evidence from the nude mice showed that the collagen component of HSE underwent remodeling within the first seven days of grafting. Clinical: All diabetic foot ulcers healed in 31.8 12.4 days. Local release of a unique combination of 15 growth factors expressed by HSE keratinocyte and fibroblast components generates closure of diabetic foot ulcers. HSE should be applied with the same surgical conditions for a skin graft (i.e., no cellulitis, no drainage, and negligible bacteria). We hypothesize that bilayered HSE generates its effect by way of the local synthesis and release of multiple growth factors in specific combination and concentration, which improves the impaired reparative process of chronic wounds.