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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Autores principales: Stephanie Arndt, Petra Unger, Anja-Katrin Bosserhoff, Mark Berneburg, Sigrid Karrer
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:0396ff122f604ca8bcd1d7b46c426ad92021-11-25T16:48:50ZThe Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo10.3390/biomedicines91115452227-9059https://doaj.org/article/0396ff122f604ca8bcd1d7b46c426ad92021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1545https://doaj.org/toc/2227-9059Cold 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.Stephanie ArndtPetra UngerAnja-Katrin BosserhoffMark BerneburgSigrid KarrerMDPI AGarticlecold atmospheric plasmalocalized sclerodermaanti-fibrosisbleomycin-induced fibrosisBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1545, p 1545 (2021)
institution DOAJ
collection DOAJ
language EN
topic cold atmospheric plasma
localized scleroderma
anti-fibrosis
bleomycin-induced fibrosis
Biology (General)
QH301-705.5
spellingShingle cold atmospheric plasma
localized scleroderma
anti-fibrosis
bleomycin-induced fibrosis
Biology (General)
QH301-705.5
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
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.
format article
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
title 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_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_sort anti-fibrotic effect of cold atmospheric plasma on localized scleroderma in vitro and in vivo
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/0396ff122f604ca8bcd1d7b46c426ad9
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