Molecular markers in patients with chronic wounds to guide surgical debridement
Molecular markers in patients with chronic wounds to guide surgical debridement
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DOI：
10.2119/2006-00054.brem
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发表时间：
2007-01-01
影响因子：
5.7
通讯作者：
Tomic-Canic, Marjana
中科院分区：
文献类型：
--
作者：
Brem, Harold;Stojadinovic, Olivera;Tomic-Canic, Marjana
慢性伤口，如静脉溃疡，以生理损伤为特征，表现为愈合延迟，导致严重并发症。外科清创是慢性伤口的常规手术，因为它能促进愈合。然而，由于与肿瘤切除不同，没有客观的生物/分子标记物来指导清创的程度，因此同一患者的手术会重复多次。为了开发可能指导外科清创的生物测定方法，我们评估了患者在清创前后伤口组织的发病机制。我们从三名患者的两个部位(未愈合的边缘(清创前)和邻近的未溃烂的皮肤(清创后))获取活检组织，并评估他们的组织学、对创伤(迁移)的生物反应和基因表达谱。我们发现，未愈合边缘的活检组织显示出不同的致病形态(过度增殖/过度角化的表皮；真皮纤维化；前胶原合成增加)。与邻近的非溃烂活检的细胞相比，来自该部位的成纤维细胞表现出迁移障碍，后者表现出形态正常和正常的迁移能力。不可愈合的边缘具有特定的、可识别的和可复制的基因表达谱。相邻的非溃烂活检组织有自己独特的可重复的基因表达谱，这意味着特定的伤口区域可以通过基因表达谱来识别。我们的结论是，慢性溃疡包含不同的细胞亚群，具有不同的愈合能力，可以利用基因表达谱来识别它们。未来，将开发分子标记来识别未受损的组织，从而使外科清创手术更加准确和有效。
Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients' wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious.