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人脐带华通氏胶间充质干细胞对单核细胞来源树突状细胞分化、成熟及内吞作用的免疫调节效应

Immunomodulatory effects of human umbilical cord Wharton's jelly-derived mesenchymal stem cells on differentiation, maturation and endocytosis of monocyte-derived dendritic cells.

作者信息

Saeidi Mohsen, Masoud Ahmad, Shakiba Yadollah, Hadjati Jamshid, Mohyeddin Bonab Mandana, Nicknam Mohammad Hossein, Latifpour Mostafa, Nikbin Behrooz

机构信息

Molecular Immunology Research Center and Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2013 Mar;12(1):37-49.

Abstract

The Wharton's jelly of the umbilical cord is believed to be a source of mesenchymal stem cells (MSCs) which can be therapeutically applied in degenerative diseases.In this study, we investigated the immunomodulatory effect of umbilical cord derived-mesenchymal stem cells (UC-MSCs) and bone marrow-derived-mesenchymal stem cells (BM-MSCs) on differentiation, maturation, and endocytosis of monocyte-derived dendritic cells in a transwell culture system under laboratory conditions. Monocytes were differentiated into immature dendritic cells (iDCs) in the presence of GM-CSF and IL-4 for 6 days and then differentiated into mature dendritic cells (mDCs) in the presence of TNF-α for 2 days. In every stage of differentiation, immature and mature dendritic cells were separately co-cultured with UC-MSCs and BM-MSCs. The findings showed that UC-MSCs and BM-MSCs inhibited strongly differentiation and maturation of dendritic cells at higher dilution ratios (1:1). The BM-MSCs and UC-MSCs showed more inhibitory effect on CD1a, CD83, CD86 expression, and dendritic cell endocytic activity, respectively. On the other hand, these cells severely up-regulated CD14 marker expression. We concluded that UC-MSCs and BM-MSCs could inhibit differentiation, maturation and endocytosis in monocyte-derived DCs through the secreted factors and free of any cell-cell contacts under laboratory conditions. As DCs are believed to be the main antigen presenting cells for naïve T cells in triggering immune responses, it would be logical that their inhibitory effect on differentiation, maturation and function can decrease or modulate immune and inflammatory responses.

摘要

脐带华通氏胶被认为是间充质干细胞(MSCs)的一个来源,这些间充质干细胞可用于治疗退行性疾病。在本研究中,我们在实验室条件下的Transwell培养系统中,研究了脐带间充质干细胞(UC-MSCs)和骨髓间充质干细胞(BM-MSCs)对单核细胞来源的树突状细胞分化、成熟和内吞作用的免疫调节作用。单核细胞在GM-CSF和IL-4存在的情况下分化为未成熟树突状细胞(iDCs)6天,然后在TNF-α存在的情况下分化为成熟树突状细胞(mDCs)2天。在分化的每个阶段,未成熟和成熟的树突状细胞分别与UC-MSCs和BM-MSCs共培养。结果表明,在较高稀释比例(1:1)下,UC-MSCs和BM-MSCs强烈抑制树突状细胞的分化和成熟。BM-MSCs和UC-MSCs分别对CD1a、CD83、CD86表达和树突状细胞内吞活性表现出更强的抑制作用。另一方面,这些细胞严重上调了CD14标志物的表达。我们得出结论,在实验室条件下,UC-MSCs和BM-MSCs可以通过分泌因子抑制单核细胞来源的树突状细胞的分化、成熟和内吞作用,且无需任何细胞间接触。由于树突状细胞被认为是幼稚T细胞触发免疫反应的主要抗原呈递细胞,因此它们对分化、成熟和功能的抑制作用可以降低或调节免疫和炎症反应,这是合乎逻辑的。

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