Department of Trauma-, Hand- and Reconstructive Surgery, Saarland University, Kirrberger Strasse, Bldng. 57, 66421, Homburg, Germany.
Mol Biol Rep. 2013 Feb;40(2):1721-33. doi: 10.1007/s11033-012-2223-6. Epub 2012 Oct 14.
Due to an increasing life expectancy in western countries, chronic wound treatment will be an emerging challenge in the next decades. Because therapies are improving slowly appropriate diagnostic tools enabling the early prediction of the healing success remain to be developed. We used a well-established in vitro assay in combination with the analysis of 27 cytokines to discriminate between fibroblasts from chronic (n = 6) and well healing (n = 8) human wounds. Proliferation and migration of the cells as well as their response to hypoxia and their behaviour in co-culture with microvascular endothelial cells were analyzed. Myofibroblast differentiation, a time-limited essential process of regular wound healing, was also quantified. Besides weaker proliferation and migration significantly higher rates of myofibroblasts were detected in chronic wounds. With respect to the cytokine release, there was a clear trend within the group of chronic wound fibroblasts, which were releasing interferon-γ, monocyte chemotactic protein-1, granulocyte-macrophage colony stimulating factor and basic fibroblast growth factor in higher amounts than fibroblasts from healing wounds. Although the overall response of both groups of fibroblasts to hypoxia and to the contact with endothelial cells was similar, especially chronic wound fibroblasts seemed to benefit from the endothelial interaction during hypoxia and displayed better migration characteristics. The study shows (1) that the assay can identify specific features of fibroblasts derived from different human wounds and (2) that wound fibroblasts are varying in their response to the chosen parameters. Thus, current therapeutic approaches and individual healing prediction might benefit from this assay.
由于西方国家预期寿命的增加,慢性伤口治疗将成为未来几十年的一个新兴挑战。由于治疗方法进展缓慢,因此需要开发适当的诊断工具,以便能够早期预测愈合成功。我们使用了一种成熟的体外检测方法,并结合了对 27 种细胞因子的分析,以区分来自慢性(n = 6)和愈合良好(n = 8)人类伤口的成纤维细胞。分析了细胞的增殖和迁移,以及它们对缺氧的反应,以及它们与微血管内皮细胞共培养的行为。成肌纤维细胞分化是正常伤口愈合的一个有限时间的必要过程,也进行了定量分析。除了增殖和迁移较弱外,慢性伤口中成肌纤维细胞的比例明显更高。就细胞因子释放而言,慢性伤口成纤维细胞组中有一个明显的趋势,它们释放的干扰素-γ、单核细胞趋化蛋白-1、粒细胞-巨噬细胞集落刺激因子和碱性成纤维细胞生长因子的量明显高于愈合伤口的成纤维细胞。尽管两组成纤维细胞对缺氧和与内皮细胞接触的总体反应相似,但慢性伤口成纤维细胞似乎在缺氧期间从内皮细胞相互作用中受益,并表现出更好的迁移特征。该研究表明:(1)该检测方法可以识别来自不同人类伤口的成纤维细胞的特定特征;(2)伤口成纤维细胞对所选参数的反应存在差异。因此,当前的治疗方法和个体愈合预测可能受益于该检测方法。