Pisciotta Alessandra, Di Tinco Rosanna, Bertani Giulia, Orlandi Giulia, Bertoni Laura, Pignatti Elisa, Orciani Monia, Sena Paola, Bertacchini Jessika, Salvarani Carlo, Carnevale Gianluca
Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy.
Front Cell Dev Biol. 2023 May 3;11:1196023. doi: 10.3389/fcell.2023.1196023. eCollection 2023.
In autoimmune diseases, particularly in systemic sclerosis and chronic periaortitis, a strict correlation between chronic inflammation and fibrosis exists. Since the currently used drugs prove mostly effective in suppressing inflammation, a better comprehension of the molecular mechanisms exerted by cell types implicated in fibro-inflammation is needed to develop novel therapeutic strategies. Mesenchymal stromal/stem cells (MSCs) are being matter of deep investigation to unveil their role in the evolution of fibrogenetic process. Several findings pointed out the controversial implication of MSCs in these events, with reports lining at a beneficial effect exerted by external MSCs and others highlighting a direct contribution of resident MSCs in fibrosis progression. Human dental pulp stem cells (hDPSCs) have demonstrated to hold promise as potential therapeutic tools due to their immunomodulatory properties, which strongly support their contribution to tissue regeneration. Our present study evaluated hDPSCs response to a fibro-inflammatory microenvironment, mimicked in vitro by a transwell co-culture system with human dermal fibroblasts, at early and late culture passages, in presence of TGF-β1, a master promoter of fibrogenesis. We observed that hDPSCs, exposed to acute fibro-inflammatory stimuli, promote a myofibroblast-to-lipofibroblast transition, likely based on BMP2 dependent pathways. Conversely, when a chronic fibro-inflammatory microenvironment is generated, hDPSCs reduce their anti-fibrotic effect and acquire a pro-fibrotic phenotype. These data provide the basis for further investigations on the response of hDPSCs to varying fibro-inflammatory conditions.
在自身免疫性疾病中，尤其是系统性硬化症和慢性主动脉周炎，慢性炎症与纤维化之间存在着密切的关联。由于目前使用的药物大多在抑制炎症方面有效，因此需要更好地理解参与纤维炎症的细胞类型所发挥的分子机制，以开发新的治疗策略。间充质基质/干细胞（MSCs）正成为深入研究的对象，以揭示它们在纤维生成过程演变中的作用。一些研究结果指出了MSCs在这些事件中的争议性影响，有报道表明外源性MSCs具有有益作用，而其他报道则强调驻留MSCs在纤维化进展中的直接作用。人牙髓干细胞（hDPSCs）因其免疫调节特性已被证明有望成为潜在的治疗工具，这有力地支持了它们对组织再生的贡献。我们目前的研究评估了hDPSCs在早期和晚期传代培养时，在存在纤维化主要促进因子TGF-β1的情况下，对由人皮肤成纤维细胞通过Transwell共培养系统在体外模拟的纤维炎症微环境的反应。我们观察到，暴露于急性纤维炎症刺激下的hDPSCs促进了肌成纤维细胞向脂成纤维细胞的转变，这可能基于BMP2依赖性途径。相反，当产生慢性纤维炎症微环境时，hDPSCs会降低其抗纤维化作用并获得促纤维化表型。这些数据为进一步研究hDPSCs对不同纤维炎症条件的反应提供了基础。
