Barbetta Cristiano, Bonomi Francesco, Lepri Gemma, Furst Daniel E, Randone Silvia Bellando, Guiducci Serena
Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, AOU Careggi, 50121 Florence, Italy.
Department of Internal Medicine, University Hospital Careggi, 50134 Florence, Italy.
Cells. 2025 Jul 3;14(13):1018. doi: 10.3390/cells14131018.
Mesenchymal stem cell (MSC) transplantation has emerged as a potential therapeutic strategy for systemic sclerosis (SSc), a rare autoimmune disease characterized by inflammation, fibrosis, and vasculopathy. Recent evidence suggests that the therapeutic benefits of MSCs do not depend directly on their ability to proliferate but rather on their capacity to release extracellular nanovesicles known as exosomes (MSC-Exos). MSC-Exos are rich in bioactive molecules such as microRNAs, which can modulate gene expression and trigger significant biological responses, playing a central role in modulating immune responses, inhibiting fibrotic pathways and promoting tissue repair and angiogenesis. Preclinical studies have demonstrated that MSC-Exos can attenuate fibrosis, modulate macrophage polarization, suppress autoreactive lymphocyte activity, and even reverse pulmonary arterial hypertension in animal models of SSc. Compared to cell-based therapies, MSC-Exos offer several advantages, including lower immunogenicity and better safety profile. This review provides an overview of the immunomodulatory, antifibrotic, and angiogenic properties of MSC-Exos and explores their potential as novel cell-free therapy for SSc.
间充质干细胞（MSC）移植已成为系统性硬化症（SSc）的一种潜在治疗策略，SSc是一种罕见的自身免疫性疾病，其特征为炎症、纤维化和血管病变。最近的证据表明，MSC的治疗益处并非直接取决于其增殖能力，而是取决于其释放称为外泌体（MSC-Exos）的细胞外纳米囊泡的能力。MSC-Exos富含生物活性分子，如微小RNA，它们可以调节基因表达并引发显著的生物学反应，在调节免疫反应、抑制纤维化途径以及促进组织修复和血管生成中发挥核心作用。临床前研究表明，在SSc动物模型中，MSC-Exos可以减轻纤维化、调节巨噬细胞极化、抑制自身反应性淋巴细胞活性，甚至逆转肺动脉高压。与基于细胞的疗法相比，MSC-Exos具有几个优点，包括较低的免疫原性和更好的安全性。本综述概述了MSC-Exos的免疫调节、抗纤维化和血管生成特性，并探讨了它们作为SSc新型无细胞疗法的潜力。
