Tissue-remodelling M2 Macrophages Recruits Matrix Metalloproteinase-9 for Cryotherapy-induced Fibrotic Resolution during Keloid Treatment
Young In Lee, Soo Min Kim, Jihee Kim, Jemin Kim, Seung Yong Song, Won Jai Lee, Ju Hee Lee
Cryotherapy is used to treat keloid scars; however, the molecular and pathological mechanisms are not clearly understood. This study retrospectively evaluated the efficacy of combined treatment with cryotherapy and intralesional triamcinolone injection (Cryo+TA) or intralesional TA monotherapy (TA) in 40 Asian patients with keloid scars. Scar improvement was assessed using the Vancouver Scar Scale and Global Improvement Scale. Clinical improvement in scars, especially reduced vascularity and redness, was significantly greater in the Cryo+TA group than in the TA group. Cryotherapy-treated and untreated keloid tissue was collected from six patients for analysis. Histologically, collagen bundles from cryotherapy-treated keloid tissue were more fibrillar and abnormal thickness was reduced. Immunohistochemical staining showed a reduced number of dermal vessels after cryotherapy. Moreover, CD163+ M2 macrophages and matrix metalloproteinase-9 (MMP-9) were significantly increased in cryotherapy-treated tissue. Double immunofluorescence staining revealed co-expression of CD163 and MMP-9. These data indicate that cryotherapy recruits tissue-remodelling M2 macrophages with accompanying MMP-9, suggesting that cryotherapy-recruited M2 macrophages function in fibrotic resolution during keloid treatment.
Superficial cryotherapy is one of the most commonly used treatment modalities for keloid scars; however, its molecular mechanism is still not completely understood. This study retrospectively evaluated the efficacy of combined treatment with cryotherapy and intralesional steroid injection or intralesional steroid injection in 40 patients. Clinical scar improvement, especially improvement in redness of scars, was significantly greater when cryotherapy was combined. Histologically, abnormal collagen bundles and dermal vessels from cryotherapy-treated keloid tissue were significantly reduced. Moreover, CD163+ M2 macrophages and matrix metalloproteinase-9 were significantly increased. These data indicate that cryotherapy-recruited macropahges supply matrix metalloproteinase-9, which function in fibrotic resolution in during keloid treatment.