Tomic-Canic Marjana, Mamber Stephen W, Stojadinovic Olivera, Lee Brian, Radoja Nadezda, McMichael John
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York 10016, USA.
Wound Repair Regen. 2007 Jan-Feb;15(1):71-9. doi: 10.1111/j.1524-475X.2006.00187.x.
ML-05, a modified form of the hemolytic and cytotoxic bacterial toxin, streptolysin O, is currently being investigated as a treatment for collagen-related disorders such as scleroderma and fibrosis. Furthermore, ML-05 may be effective in promoting wound healing and alleviating the formation of hypertrophic scars and keloids. To investigate the effects of ML-05 on wound-healing processes, in vitro wound-healing scratch assays (using human primary epidermal keratinocytes and dermal fibroblasts) and a human skin organ culture wound model were utilized. ML-05 markedly enhanced keratinocyte migration and proliferation in wound scratch assays. ML-05 did not affect either proliferation or migration of dermal fibroblasts, indicating that ML-05's effects on cell migration/proliferation may be keratinocyte-specific. ML-05 was tested in a dose-dependent manner in a skin organ culture wound model using two different application methods: Through the culture media (dermal exposure) or direct topical treatment of the wound surface. ML-05 was found to accelerate wound healing as measured by reepithelialization, particularly after topical application. Therefore, ML-05 may have potential as a wound-healing agent that promotes reepithelialization through stimulation of keratinocyte migration and proliferation.
ML-05是溶血和细胞毒性细菌毒素链球菌溶血素O的一种改良形式,目前正作为治疗硬皮病和纤维化等胶原相关疾病的一种疗法进行研究。此外,ML-05在促进伤口愈合以及减轻增生性瘢痕和瘢痕疙瘩的形成方面可能有效。为了研究ML-05对伤口愈合过程的影响,采用了体外伤口愈合划痕试验(使用人原代表皮角质形成细胞和真皮成纤维细胞)以及人皮肤器官培养伤口模型。在伤口划痕试验中,ML-05显著增强了角质形成细胞的迁移和增殖。ML-05对真皮成纤维细胞的增殖或迁移均无影响,这表明ML-05对细胞迁移/增殖的作用可能具有角质形成细胞特异性。在皮肤器官培养伤口模型中,使用两种不同的应用方法以剂量依赖方式对ML-05进行了测试:通过培养基(真皮暴露)或直接局部处理伤口表面。通过再上皮化测量发现,ML-05可加速伤口愈合,尤其是在局部应用后。因此,ML-05可能具有作为一种伤口愈合剂的潜力,通过刺激角质形成细胞的迁移和增殖来促进再上皮化。