Multiple sclerosis (MS) is a central nervous system (CNS) degenerative disorder which is caused by a targeted autoimmune-mediated attack on myelin proteins. Previously, mesenchymal stem cells were considered as a novel and successful treatment of MS. One of the underlying mechanisms behind their immunomodulatory function is the release of extracellular vesicles, particularly exosomes. In this study, we aimed to evaluate the suppressive efficacy of MSCs and their exosomes on the proliferation of peripheral mononuclear blood cells (PBMC) in relapsing-remitting MS (RRMS) patients and healthy subjects. To do, mesenchymal stem cells were derived from human umbilical cord tissues and used for exosome isolation through ultracentrifugation. Suppressive function of MSCs and MSC-derived exosomes was examined in a coculture with CFSE-labelled PBMCs in vitro. PBMC proliferation of the patients and healthy individuals was measured using flow cytometry. We first demonstrated that proliferation of PBMCs decreased in the presence of MSCs and suppression was more efficient by MSC-derived exosomes, with a minimum alloreaction rate. However, suppression capacity of MSCs and their exosomes significantly decreased during extensive sub-culturing. The present study showed that MSC-derived exosomes as an effective cell-free therapy could prevent proliferation of PBMCs. However, further evaluations are need to move towards a functional approach that can be translated to the clinic.

中文翻译：

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脐带间充质干细胞及其释放的外来体抑制多发性硬化症中活化的PBMC的增殖

多发性硬化症（MS）是中枢神经系统（CNS）退化性疾病，由对髓磷脂蛋白的靶向自身免疫介导的攻击引起。以前，间充质干细胞被认为是一种新颖而成功的MS治疗方法。它们的免疫调节功能背后的潜在机制之一是细胞外小泡，特别是外泌体的释放。在这项研究中，我们旨在评估MSCs及其外泌体对复发缓解型MS（RRMS）患者和健康受试者外周血单个核细胞（PBMC）增殖的抑制作用。为此，间充质干细胞来源于人的脐带组织，并用于通过超速离心分离外来体。在体外与CFSE标记的PBMC共培养中检查了MSC和MSC来源的外来体的抑制功能。使用流式细胞术测量患者和健康个体的PBMC增殖。我们首先证明了在存在MSC的情况下PBMC的增殖减少了，而MSC衍生的外泌体的抑制作用更为有效，其最小的变态反应率。但是，在大量传代培养过程中，MSCs及其外泌体的抑制能力显着下降。本研究表明，MSC来源的外泌体作为一种有效的无细胞疗法可以预防PBMC的增殖。但是，还需要进一步评估，以朝着可以转化为临床的功能方法迈进。具有最小的变态反应率。但是，在大量传代培养过程中，MSCs及其外泌体的抑制能力显着下降。本研究表明，MSC来源的外泌体作为一种有效的无细胞疗法可以预防PBMC的增殖。但是，需要进一步评估以朝着可以转化为临床的功能方法发展。具有最小的变态反应率。但是，在大量传代培养过程中，MSCs及其外泌体的抑制能力显着下降。本研究表明，MSC来源的外泌体作为一种有效的无细胞疗法可以预防PBMC的增殖。但是，需要进一步评估以朝着可以转化为临床的功能方法发展。