Laboratory for Cardiac and Thoracic Diagnosis, Regeneration and Applied Immunology, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria; Aposcience AG (FN 308089y), Dresdner Straße 87/A21, Vienna, Austria.
Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria.
Matrix Biol. 2022 Apr;108:55-76. doi: 10.1016/j.matbio.2022.03.001. Epub 2022 Mar 10.
Keloids are disfiguring, hypertrophic scars with yet poorly understood pathomechanisms, which could lead to severe functional impairments. Here we analyzed the characteristics of keloidal cells by single cell sequencing and discovered the presence of an abundant population of Schwann cells that persisted in the hypertrophic scar tissue after wound healing. In contrast to normal skin, keloidal Schwann cells show a unique, pro-fibrotic phenotype. Our data support the hypothesis that keloidal Schwann cells contribute to the formation of the extracellular matrix and are able to affect M2 polarization of macrophages. Indeed, we show that macrophages in keloids predominantly display a M2 polarization and produce factors that inhibit Schwann cell differentiation. This study suggests the contribution of a Schwann cell - macrophage cross-talk to the continuous expansion of keloids, and that targeting Schwann cells might represent an interesting novel treatment option for keloids.
瘢痕疙瘩是一种畸形的、增生性瘢痕,其发病机制尚不清楚,可能导致严重的功能障碍。在这里,我们通过单细胞测序分析了瘢痕疙瘩细胞的特征,发现了一种丰富的雪旺细胞群体,它们在创伤愈合后仍然存在于增生性瘢痕组织中。与正常皮肤相比,瘢痕疙瘩雪旺细胞表现出独特的、促纤维化表型。我们的数据支持这样一种假设,即瘢痕疙瘩雪旺细胞有助于细胞外基质的形成,并能够影响巨噬细胞的 M2 极化。事实上,我们表明,瘢痕疙瘩中的巨噬细胞主要表现出 M2 极化,并产生抑制雪旺细胞分化的因子。这项研究表明,雪旺细胞-巨噬细胞相互作用对瘢痕疙瘩的持续扩张有贡献,而针对雪旺细胞可能是一种治疗瘢痕疙瘩的新的治疗选择。