Streptolysin O enhances keratinocyte migration and proliferation and promotes skin organ culture wound healing in vitro

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.