Brem Harold, Stojadinovic Olivera, Diegelmann Robert F, Entero Hyacinth, Lee Brian, Pastar Irena, Golinko Michael, Rosenberg Harvey, Tomic-Canic Marjana
Columbia University College of Physicians and Surgeons, Department of Surgery, Wound Healing and Vascular Biology Laboratory, New York, NY, USA.
Mol Med. 2007 Jan-Feb;13(1-2):30-9. doi: 10.2119/2006-00054.Brem.
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.
慢性伤口，如静脉溃疡，其特征是生理功能受损，表现为愈合延迟，导致严重的发病率。手术清创术常用于慢性伤口，因为它能刺激愈合。然而，由于与肿瘤切除不同，没有客观的生物学/分子标志物来指导清创范围，所以同一患者需要多次进行该手术。为了开发可能指导手术清创的生物测定法，我们评估了患者伤口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获取活检样本，即不愈合边缘（清创前）和静脉溃疡相邻的未溃疡皮肤（清创后），并评估了它们的组织学、对创伤的生物学反应（迁移）和基因表达谱。我们发现，来自不愈合边缘的活检样本呈现出独特的致病形态（增生性/角化过度的表皮；真皮纤维化；前胶原合成增加）。与来自相邻未溃疡活检样本的细胞相比，源自该部位的成纤维细胞迁移能力受损，后者形态正常且迁移能力正常。不愈合边缘具有特定的、可识别的和可重复的基因表达谱。相邻的未溃疡活检样本有其自身独特的可重复基因表达谱，这表明特定伤口区域可通过基因表达谱分析来识别。我们得出结论，慢性溃疡包含具有不同愈合能力的不同细胞亚群，基因表达谱分析可用于识别它们。未来将会开发分子标志物来识别未受损组织，从而使手术清创更准确、更有效。
