Abstract
Cold Atmospheric Plasma (CAP) has shown promising results in the treatment of various skin diseases. The therapeutic effect of CAP on localized scleroderma (LS), however, has not yet been evaluated. We investigated the effects of CAP on LS by comparing human normal fibroblasts (hNF), human TGF-β-activated fibroblasts (hAF), and human localized scleroderma-derived fibroblasts (hLSF) after direct CAP treatment, co-cultured with plasma-treated human epidermal keratinocytes (hEK) and with an experimental murine model of scleroderma. In hAF and hLSF, 2 min CAP treatment with the MicroPlaSterβ® plasma torch did not affect pro-fibrotic gene expression of alpha smooth muscle actin, fibroblast activating protein, and collagen type I, however, it promoted re-expression of matrix metalloproteinase 1. Functionally, CAP treatment reduced cell migration and stress fiber formation in hAF and hLSF. The relevance of CAP treatment was confirmed in an in vivo model of bleomycin-induced dermal fibrosis. In this model, CAP-treated mice showed significantly reduced dermal thickness and collagen deposition as well as a decrease in both alpha smooth muscle actin-positive myofibroblasts and CD68-positive macrophages in the affected skin in comparison to untreated fibrotic tissue. In conclusion, this study provides the first evidence for the successful use of CAP for treating LS and may be the basis for clinical trials including patients with LS.
Highlights
Accepted: 24 October 2021Localized scleroderma (LS)— termed morphea—is a rare chronic inflammatory disease of the collagenous connective tissue with an incidence rate ranging from 0.4 to2.7/100,000/year [1,2]
This study investigated the effect of Cold Atmospheric Plasma (CAP) treatment on localized scleroderma (LS) by means of different cell culture models with different fibroblasts and an in vivo murine model of bleomycin (BLM)-induced fibrosis
Human normal fibroblasts isolated from the dermis of healthy donors were treated with transforming growth factor β (TGF-β) to obtain an activated myofibroblast-like phenotype. human localized scleroderma-derived fibroblasts (hLSF) were isolated from the dermis of patients with localized scleroderma (LS). human TGF-β-activated fibroblasts (hAF) and hLSF were used as in vitro models for the investigation of LS and were compared with hNF
Summary
Localized scleroderma (LS)— termed morphea—is a rare chronic inflammatory disease of the collagenous connective tissue with an incidence rate ranging from 0.4 to. 2.7/100,000/year [1,2]. LS is characterized by skin thickening with increased quantities of collagen in the affected lesion [3]. According to Peterson et al, the LS entity is subdivided into linear, plaque, deep, bullous and generalized morphea [2]. Apart from the skin, neighboring structures such as adipose tissue, muscles, joints and bones can be affected, depending on the subtype of LS. In contrast to systemic sclerosis (SS), internal organs are not involved. Collagen balance regulated by dermal fibroblasts plays an important role in LS. The transforming growth factor β (TGF-β) exerts a major influence on the collagen metabolism and has been implicated in research as a crucial factor for the development of fibrosis [4,5]
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