Arndt Stephanie, Unger Petra, Bosserhoff Anja-Katrin, Berneburg Mark, Karrer Sigrid
Department of Dermatology, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany.
Institute of Biochemistry, University of Erlangen-Nuernberg (FAU), 91054 Erlangen, Germany.
Biomedicines. 2021 Oct 26;9(11):1545. doi: 10.3390/biomedicines9111545.
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.
冷大气等离子体（CAP）在多种皮肤疾病的治疗中已显示出有前景的结果。然而，CAP对局限性硬皮病（LS）的治疗效果尚未得到评估。我们通过比较直接CAP处理后的人正常成纤维细胞（hNF）、人转化生长因子-β激活的成纤维细胞（hAF）和人局限性硬皮病来源的成纤维细胞（hLSF），与经血浆处理的人表皮角质形成细胞（hEK）共培养以及与硬皮病实验小鼠模型，来研究CAP对LS的影响。在hAF和hLSF中，使用MicroPlaSterβ等离子体喷枪进行2分钟的CAP处理并不影响α平滑肌肌动蛋白、成纤维细胞激活蛋白和I型胶原的促纤维化基因表达，然而，它促进了基质金属蛋白酶1的重新表达。在功能上，CAP处理减少了hAF和hLSF中的细胞迁移和应力纤维形成。CAP处理的相关性在博来霉素诱导的皮肤纤维化体内模型中得到证实。在该模型中，与未处理的纤维化组织相比，CAP处理的小鼠在受影响皮肤中的真皮厚度和胶原沉积显著减少，同时α平滑肌肌动蛋白阳性肌成纤维细胞和CD68阳性巨噬细胞均减少。总之，本研究为成功使用CAP治疗LS提供了首个证据，可能是包括LS患者在内的临床试验的基础。
