Formoso Sergio Oliveira, Chaleix Vincent, Baccile Niki, Helary Christophe
Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Chimie de la Matière Condensée de Paris, LCMCP, Paris F-75005, France.
Université de Limoges, Faculté des sciences et techniques, Laboratoire LABCiS - UR 22722, Limoges 87060, France.
Toxicol Rep. 2024 Dec 10;14:101862. doi: 10.1016/j.toxrep.2024.101862. eCollection 2025 Jun.
Fibroblasts are considered a key player in the wound healing process. Although this cellular family is constituted by several distinct subtypes, dermal fibroblasts are crucial thanks to their ability to secrete pro-regenerative growth factors, extracellular matrix (ECM) proteins and their immune and anti-inflammatory role. Sophorolipids (SL), sophorosides (SS) and glucolipids (G), mono-unsaturated (C18:1) or saturated (C18:0), glycolipids derived from microbial fermentation of wild type or engineered yeast , constitute a novel sustainable class of bio-based chemicals with interesting physicochemical characteristics, which allow them to form soft diverse structures from hydrogels to vesicles, micelles or complex coacervates with potential interest in skin regeneration applications. In this study, we first tested the cytocompatibility of a broad set of molecules from this family on normal human dermal fibroblasts (NHDF). Our results show that, up to an upper threshold (0.1 % w/v), the microbial glycolipids (SL-C18:1, G-C18:1, SS-C18:1, SL-C18:0 and G-C18:0) under study were able to sustain cell growth. Furthermore, we selected the least cytotoxic glycolipids (SL-C18:1, SS-C18:1, SL-C18:0) to study their potential to promote wound healing by measuring the gene expression of several key skin regeneration markers (i.e. collagen, elastin, transforming growth factor β, fibroblast growth factor …) using qPCR. Unfortunately, none of these glycolipids modulated the gene expression of molecules involved in tissue repair. However, this study aims to encourage the community to test this novel class of molecules for novel high-end biomedical applications.
Biosurfactants prepared by microbial fermentation are natural amphiphiles of growing importance, with the goal of replacing synthetic surfactants in commercial formulations. However, their cytotoxicity profile is still poorly known, especially for new molecules like single-glucose lipids or bolaform sophorolipids. This wants to contribute to all those applications, which could be developed with biosurfactants in contact with the skin (cosmetics, wound healing). We test the cytotoxicity of five structurally-related molecules (C18:1 and C18:0 sophorolipids, C18:1 and C18:0 single-glucose lipids, C18:1 di-sophoroside) against normal human dermal fibroblasts (NHDF) and evaluate the metabolic activity of the least toxic among them. To the best of our knowledge, cytotoxicity of these molecules, and of microbial biosurfactants in general, was never tested against NHDF.
成纤维细胞被认为是伤口愈合过程中的关键参与者。尽管这个细胞家族由几种不同的亚型组成，但真皮成纤维细胞至关重要，这得益于它们分泌促再生生长因子、细胞外基质（ECM）蛋白的能力以及它们的免疫和抗炎作用。槐糖脂（SL）、槐糖苷（SS）和糖脂（G），单不饱和（C18:1）或饱和（C18:0），源自野生型或工程酵母微生物发酵的糖脂，构成了一类新型的可持续生物基化学品，具有有趣的物理化学特性，这使它们能够形成从水凝胶到囊泡、胶束或复合凝聚层等多样的柔软结构，在皮肤再生应用中具有潜在的应用价值。在本研究中，我们首先测试了该家族中一系列广泛分子对正常人真皮成纤维细胞（NHDF）的细胞相容性。我们的结果表明，在所研究的微生物糖脂（SL-C18:1、G-C18:1、SS-C18:1、SL-C18:0和G-C18:0）中，直至上限阈值（0.1% w/v），它们都能够维持细胞生长。此外，我们选择了细胞毒性最小的糖脂（SL-C18:1、SS-C18:1、SL-C18:0），通过使用qPCR测量几种关键皮肤再生标志物（即胶原蛋白、弹性蛋白、转化生长因子β、成纤维细胞生长因子……）的基因表达，来研究它们促进伤口愈合的潜力。不幸的是，这些糖脂均未调节参与组织修复的分子的基因表达。然而，本研究旨在鼓励该领域测试这类新型分子用于新型高端生物医学应用。
通过微生物发酵制备的生物表面活性剂是日益重要的天然两亲分子，目标是在商业配方中替代合成表面活性剂。然而，它们的细胞毒性特征仍然鲜为人知，尤其是对于像单葡萄糖脂或bola型槐糖脂这样的新分子。这有助于所有那些可以用与皮肤接触的生物表面活性剂开发的应用（化妆品、伤口愈合）。我们测试了五种结构相关分子（C18:1和C18:0槐糖脂、C18:1和C18:0单葡萄糖脂、C18:1二槐糖苷）对正常人真皮成纤维细胞（NHDF）的细胞毒性，并评估了其中毒性最小的分子的代谢活性。据我们所知，这些分子以及一般微生物生物表面活性剂的细胞毒性从未针对NHDF进行过测试。
