The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo

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-act...

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Main Authors: Stephanie Arndt, Petra Unger, Anja-Katrin Bosserhoff, Mark Berneburg, Sigrid Karrer
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/9/11/1545
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author Stephanie Arndt
Petra Unger
Anja-Katrin Bosserhoff
Mark Berneburg
Sigrid Karrer
author_facet Stephanie Arndt
Petra Unger
Anja-Katrin Bosserhoff
Mark Berneburg
Sigrid Karrer
author_sort Stephanie Arndt
collection DOAJ
description 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<sup>®</sup> 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.
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spelling doaj.art-0396ff122f604ca8bcd1d7b46c426ad92023-11-22T22:29:49ZengMDPI AGBiomedicines2227-90592021-10-01911154510.3390/biomedicines9111545The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In VivoStephanie Arndt0Petra Unger1Anja-Katrin Bosserhoff2Mark Berneburg3Sigrid Karrer4Department of Dermatology, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, GermanyDepartment of Dermatology, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, GermanyInstitute of Biochemistry, University of Erlangen-Nuernberg (FAU), 91054 Erlangen, GermanyDepartment of Dermatology, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, GermanyDepartment of Dermatology, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, GermanyCold 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<sup>®</sup> 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.https://www.mdpi.com/2227-9059/9/11/1545cold atmospheric plasmalocalized sclerodermaanti-fibrosisbleomycin-induced fibrosis
spellingShingle Stephanie Arndt
Petra Unger
Anja-Katrin Bosserhoff
Mark Berneburg
Sigrid Karrer
The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo
Biomedicines
cold atmospheric plasma
localized scleroderma
anti-fibrosis
bleomycin-induced fibrosis
title The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo
title_full The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo
title_fullStr The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo
title_full_unstemmed The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo
title_short The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo
title_sort anti fibrotic effect of cold atmospheric plasma on localized scleroderma in vitro and in vivo
topic cold atmospheric plasma
localized scleroderma
anti-fibrosis
bleomycin-induced fibrosis
url https://www.mdpi.com/2227-9059/9/11/1545
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