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...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-10-01
|
Series: | Biomedicines |
Subjects: | |
Online Access: | https://www.mdpi.com/2227-9059/9/11/1545 |
_version_ | 1827677208194318336 |
---|---|
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. |
first_indexed | 2024-03-10T05:40:52Z |
format | Article |
id | doaj.art-0396ff122f604ca8bcd1d7b46c426ad9 |
institution | Directory Open Access Journal |
issn | 2227-9059 |
language | English |
last_indexed | 2024-03-10T05:40:52Z |
publishDate | 2021-10-01 |
publisher | MDPI AG |
record_format | Article |
series | Biomedicines |
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 |
work_keys_str_mv | AT stephaniearndt theantifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT petraunger theantifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT anjakatrinbosserhoff theantifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT markberneburg theantifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT sigridkarrer theantifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT stephaniearndt antifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT petraunger antifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT anjakatrinbosserhoff antifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT markberneburg antifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo AT sigridkarrer antifibroticeffectofcoldatmosphericplasmaonlocalizedsclerodermainvitroandinvivo |