Wound chronicity and fibroblast senescence--implications for treatment.
Wound chronicity and fibroblast senescence--implications for treatment.
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DOI：
10.1111/j.1742-4801.2005.00149.x
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发表时间：
2005-12-01
影响因子：
3.1
通讯作者：
Phillips, Tania J
中科院分区：
文献类型：
--
作者：
Harding, Keith G;Moore, Keith;Phillips, Tania J
一部分慢性伤口不能响应于标准治疗而愈合。对于下肢静脉溃疡，治疗开始前持续时间较长与压迫治疗的愈合反应较差之间存在相关性。愈合伤口微环境和非愈合慢性伤口微环境之间的差异表明存在许多潜在的机制来损害愈合。一个贡献机制可能是抑制成纤维细胞增殖和诱导应激诱导的过早衰老表型的慢性伤口中发现的持续炎症。衰老的成纤维细胞表现出细胞外基质降解表型，导致伤口慢性化。超过15%的衰老成纤维细胞的积累已被描述为超过其伤口变得难以愈合的阈值。衰老的比率：因此，非衰老细胞对于确定对治疗的反应是关键的，并且调节该比例以有利于非衰老细胞的连续疗法可能提高治疗愈合率。许多组织工程真皮替代品含有非衰老成纤维细胞，除了释放生长因子和逆转慢性伤口渗出物的抗增殖活性外，还可以向伤口环境提供细胞。认识到成纤维细胞衰老在伤口慢性化中的作用，可以识别对这些产品有积极反应的伤口。
A proportion of chronic wounds fail to heal in response to standard therapy. For venous leg ulcers, a correlation exists between longer duration before treatment initiation and poor healing response to compression therapy. Differences identified between the healing wound microenvironment and that of the non healing chronic wound suggests that many potential mechanisms exist to impair healing. One contributory mechanism may be inhibition of fibroblast proliferation and induction of a stress-induced premature senescence phenotype by the continuing inflammation found in chronic wounds. Senescent fibroblasts exhibit an extracellular matrix degradative phenotype that contributes to wound chronicity. Accumulation of greater than 15% senescent fibroblasts has been described as a threshold beyond which wounds become hard to heal. The ratio of senescent : non senescent cells is therefore critical to determining response to treatment, and adjunctive therapies that modulate this ratio in favour of non senescent cells are likely to enhance therapeutic healing rates. A number of tissue-engineered dermal replacements contain non senescent fibroblasts and can donate cells to the wound environment additional to releasing growth factors and reversing the antiproliferative activity of chronic wound exudate. Recognition of the role of fibroblast senescence in wound chronicity may allow for identification of those wounds that will respond positively to these products.