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人间充质干细胞条件培养基和间充质来源外泌体对单核细胞的免疫调节作用

Immunoregulatory impact of human mesenchymal-conditioned media and mesenchymal derived exosomes on monocytes.

作者信息

Tokhanbigli Samaneh, Baghaei Kaveh, Asadirad Ali, Hashemi Seyed Mahmoud, Asadzadeh-Aghdaei Hamid, Zali Mohammad Reza

机构信息

Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Mol Biol Res Commun. 2019 Jun;8(2):79-89. doi: 10.22099/mbrc.2019.33346.1397.

Abstract

Mesenchymal stem cells (MSCs) are well known due to their immunomodulatory effect, but the exact mechanisms have not been defined. Several studies demonstrated that the exerted immunoregulatory effect of these cells could be mediated by paracrine factors to illustrate, cytokines, chemokine, and among which, extracellular vesicles are one of them to play a crucial role. Moreover, it is assumed that extracellular vesicles are an essential player in intracellular communication by transferring their component. In this respect, the efficiency of conditioned media and exosomes was compared to illustrate a practical approach to cell-free based therapies. In the current study, we investigated the effect of both MSCs conditioned media (MSC-CM) and MSCs-derived exosomes on the expression of pro-inflammatory and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCs). In this regard, isolated PBMCs were treated with MSC-CM and MSC-derived exosome as separated groups. Expression of inflammatory and anti-inflammatory markers was evaluated by Real-time PCR and ELISA. The immunoregulatory effect of MSC-CM on pro-inflammatory and anti-inflammatory genes, such as IL-12b, iNOS, EGR-2, IL-10 with an exception in case of IL-6 was more significant. Whereas in protein levels IL-10 showed the most substantial difference in exosome treated groups. It could be assumed that MSC-CM has more immunoregulatory impact on monocyte in contrast with exosomes.Taken together, by considering the recent approaches to cell-free therapy and the immunoregulatory impact of MSCs, yet relatively little is known about the efficacy of human-MSC-CM and secreted exosome compared with each other.

摘要

间充质干细胞(MSCs)因其免疫调节作用而广为人知,但其确切机制尚未明确。多项研究表明,这些细胞发挥的免疫调节作用可能由旁分泌因子介导,例如细胞因子、趋化因子,其中细胞外囊泡在其中发挥关键作用。此外,据推测细胞外囊泡通过传递其成分在细胞内通讯中起着重要作用。在这方面,比较了条件培养基和外泌体的效率,以阐明一种基于无细胞疗法的实用方法。在本研究中,我们研究了间充质干细胞条件培养基(MSC-CM)和间充质干细胞衍生的外泌体对外周血单核细胞(PBMCs)中促炎和抗炎细胞因子表达的影响。在这方面,将分离的PBMCs作为单独的组用MSC-CM和间充质干细胞衍生的外泌体进行处理。通过实时PCR和ELISA评估炎症和抗炎标志物的表达。MSC-CM对促炎和抗炎基因,如IL-12b、iNOS、EGR-2、IL-10(IL-6情况除外)的免疫调节作用更为显著。而在蛋白水平上,IL-10在外泌体处理组中显示出最显著的差异。可以假设,与外泌体相比,MSC-CM对单核细胞具有更强的免疫调节作用。综上所述,考虑到最近的无细胞治疗方法以及间充质干细胞的免疫调节作用,与彼此相比,关于人MSC-CM和分泌的外泌体的功效仍知之甚少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d1c/6715264/ed4f8e96392e/mbrc-8-079-g001.jpg

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