Dedier Marianne, Magne Brice, Nivet Muriel, Banzet Sébastien, Trouillas Marina
French Armed-forces Biomedical Research Institute (IRBA), Clamart, France.
UMR-MD-U1197, Inserm, Villejuif, France.
Front Cell Dev Biol. 2023 Sep 7;11:1244120. doi: 10.3389/fcell.2023.1244120. eCollection 2023.
Despite several advances in the field of regenerative medicine, clinical management of extensive skin wounds or burns remains a major therapeutic issue. During the past few years, Mesenchymal Stromal Cells (MSCs) have emerged as a novel therapeutic tool to promote tissue repair through their anti-inflammatory, pro-trophic and pro-remodeling effects. They exert their biological activity mainly via the secretion of soluble bioactive molecules such as cytokines, growth factors, proteins and microRNAs which can be encapsulated within extracellular vesicles (EV). The recent discovery of their high plasticity to external stimuli has fostered the development of new targeted therapies known as priming strategies, to enhance their potential. Our team recently showed that Interleukin-1β (IL-1β)-primed gingival MSCs promote wound healing and epidermal engraftment , and through their secreted products that contain extracellular vesicles. In the present work, we investigated whether two common sources of MSCs, gingiva and bone marrow, could respond similarly to IL-1β to favor pro-healing capabilities of their secretome. We showed that both primed-MSC sources, or their related secreted products, are able to reduce inflammation in LPS-challenged human monocytic THP-1 cell line. IL-1β priming enhanced MSC secretion of wound healing-related growth factors, cytokines and miRNAs in both sources. Among them, interleukin 6 was shown to be involved in the anti-inflammatory effect of MSC secreted products. Overall, these results underline the pro-healing properties of both MSC sources and their secretome upon IL-1β priming and their potential to improve the current medical treatment of severe wounds.
尽管再生医学领域取得了一些进展，但大面积皮肤创伤或烧伤的临床治疗仍然是一个重大的治疗难题。在过去几年中，间充质基质细胞（MSCs）已成为一种新型治疗工具，通过其抗炎、促营养和促重塑作用来促进组织修复。它们主要通过分泌可溶性生物活性分子（如细胞因子、生长因子、蛋白质和微小RNA）发挥生物学活性，这些分子可以封装在细胞外囊泡（EV）中。最近发现它们对外部刺激具有高度可塑性，这促进了被称为引发策略的新靶向疗法的发展，以增强其潜力。我们的团队最近表明，白细胞介素-1β（IL-1β）引发的牙龈间充质干细胞通过其含有细胞外囊泡的分泌产物促进伤口愈合和表皮植入。在本研究中，我们调查了间充质干细胞的两个常见来源，即牙龈和骨髓，是否能对IL-1β做出类似反应，以增强其分泌组的促愈合能力。我们发现，两种引发的间充质干细胞来源或其相关分泌产物都能够减轻脂多糖刺激的人单核细胞THP-1细胞系中的炎症。IL-1β引发增强了两种来源中间充质干细胞分泌与伤口愈合相关的生长因子、细胞因子和微小RNA的能力。其中，白细胞介素6被证明参与了间充质干细胞分泌产物的抗炎作用。总体而言，这些结果强调了两种间充质干细胞来源及其分泌组在IL-1β引发后的促愈合特性，以及它们改善当前严重伤口医学治疗的潜力。
