Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran.
Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran AND Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Iran J Allergy Asthma Immunol. 2024 May 27;23(3):288-298. doi: 10.18502/ijaai.v23i3.15638.
Mesenchymal stem cells (MSCs) are a potential cell therapy candidate for autoimmune and inflammatory diseases due to their multilineage capacity and immune modulating function. MSCs exert immunomodulatory effects on target cells through the secretion of exosomes. Inflammatory conditions such as Toll-like receptors (TLRs) engagement can change the biological functions and immunomodulatory activities of MSCs and the contents of exosomes derived from MSCs are changed. Regulatory T-cells (Treg) are crucial for maintaining immune cell homeostasis and self-tolerance. Our study aimed to investigate the impact of isolated exosomes from hWJ-MSCs that were treated with Poly (I:C) on regulatory CD4 CD25 Foxp3 T-cells. MSCs were harvested from human umbilical cord Wharton's Jelly by explant method. Stem cells were treated by Polyinosinic-polycytidylic acid sodium salt (Poly (I:C)) for 48 hours. Exosomes were extracted from supernatant of cells and Scanning electron microscopy (SEM) and Dynamic light scattering (DLS) were performed for them. Peripheral blood mononuclear cells (PBMCs) isolated from the healthy donors were stimulated with PHA (Phytohemagglutinin) and co-cultured with Poly (I:C) treated hWJ-MSCs derived exosome and untreated hWJ-MSCs derived exosome or without hWJ-MSCs-derived exosome for 6 days. Then, frequency of CD4+CD25+ Foxp3+ regulatory T cells was measured by flow cytometry. Our results showed that exosomes isolated from Poly (I:C) treated hWJ-MSCs significantly increased frequency of CD4+CD25+ Foxp3+ regulatory T cells compared to the untreated hWJ-MSCs derived exosome group and control group. Stimulation by TLR3 improved the anti-inflammatory features of exosomes that were derived from hWJ-MSCs by increasing the frequency of Treg cells.
间充质干细胞（MSCs）因其多能性和免疫调节功能而成为自身免疫和炎症性疾病的潜在细胞治疗候选物。MSCs 通过分泌外泌体对靶细胞发挥免疫调节作用。炎症状态如 Toll 样受体（TLRs）的激活可以改变 MSCs 的生物学功能和免疫调节活性，以及源自 MSCs 的外泌体的内容物。调节性 T 细胞（Treg）对于维持免疫细胞内稳态和自身耐受至关重要。我们的研究旨在探讨用 Poly（I：C）处理的分离的 hWJ-MSCs 外泌体对调节性 CD4+CD25+Foxp3+T 细胞的影响。MSCs 采用组织块法从人脐带华通氏胶中分离。用聚肌苷酸-聚胞苷酸钠（Poly（I：C））处理干细胞 48 小时。从细胞上清液中提取外泌体，并进行扫描电子显微镜（SEM）和动态光散射（DLS）分析。从健康供体中分离外周血单个核细胞（PBMCs），用植物血凝素（PHA）刺激，并与 Poly（I：C）处理的 hWJ-MSCs 衍生的外泌体、未处理的 hWJ-MSCs 衍生的外泌体或无 hWJ-MSCs 衍生的外泌体共同培养 6 天。然后，通过流式细胞术测量 CD4+CD25+Foxp3+调节性 T 细胞的频率。我们的结果表明，与未处理的 hWJ-MSCs 衍生的外泌体组和对照组相比，来自 Poly（I：C）处理的 hWJ-MSCs 的外泌体显著增加了 CD4+CD25+Foxp3+调节性 T 细胞的频率。TLR3 的刺激通过增加 Treg 细胞的频率，增强了源自 hWJ-MSCs 的外泌体的抗炎特征。
