title: 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.
authors.affiliation: The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Marjana
authors.initials: M
authors.lastname: Tomic-Canic
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Mamber
authors.forename: Olivera
authors.initials: O
authors.lastname: Stojadinovic
authors.forename: Brian
authors.initials: B
authors.lastname: Lee
authors.forename: Nadezda
authors.initials: N
authors.lastname: Radoja
authors.forename: John
authors.initials: J
authors.lastname: McMichael
mesh_terms: D001426:Bacterial Proteins / Q000494:pharmacology; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D009924:Organ Culture Techniques; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D013301:Streptolysins / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D014950:Wounds, Penetrating / Q000503:physiopathology
chemical_list: D001426:Bacterial Proteins; D013301:Streptolysins; C025964:streptolysin O