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Streptolysin O enhances keratinocyte migration and proliferation and promotes skin organ culture wound healing in vitro
Authors:Marjana Tomic-Canic  PhD  ; Stephen W Mamber  PhD  ; Olivera Stojadinovic  MD  ; Brian Lee  MSc  ; Nadezda Radoja  PhD  ; John McMichael  PhD
Institution:The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York 10016, USA.
Abstract: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.
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