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种植在β-磷酸三钙中的颌骨骨膜细胞抑制树突状细胞成熟。

Jaw Periosteal Cells Seeded in Beta-Tricalcium Phosphate Inhibit Dendritic Cell Maturation.

机构信息

Department of Oral and Maxillofacial Surgery, University Hospital Tübingen, Osianderstr 2-8, 72076 Tübingen, Germany.

出版信息

Biomolecules. 2020 Jun 10;10(6):887. doi: 10.3390/biom10060887.

Abstract

Mesenchymal stem cells (MSCs) have gained attraction not only in the field of regenerative medicine but also in the field of autoimmune disease therapies or organ transplantation due to their immunoregulatory and/or immunosuppressive features. Dendritic cells (DCs) play a crucial role in initiating and regulating immune reactions by promoting antigen-specific T cell activation. In this study, we investigated the effect of human jaw periosteal progenitor cells (JPCs) seeded in beta-tricalcium phosphate (β-TCP) scaffolds on monocyte-derived DC differentiation. Significantly lower numbers of differentiated DCs were observed in the presence of normal (Co) and osteogenically induced (Ob) JPCs-seeded β-TCP constructs. Gene expression analysis revealed significantly lower interleukin-12 subunit p35 (IL-12p35) and interleukin-12 receptor beta 2 (IL-12Rβ2) and pro-inflammatory cytokine interferon-gamma (IFN-γ) levels in DCs under Ob conditions, while interleukin-8 (IL-8) gene levels were significantly increased. Furthermore, in the presence of JPCs-seeded β-TCP constructs, interleukin-10 (IL-10) gene expression was significantly induced in DCs, particularly under Ob conditions. Analysis of DC protein levels shows that granulocyte-colony stimulating factor (G-CSF) was significantly upregulated in coculture groups. Our results indicate that undifferentiated and osteogenically induced JPCs-seeded β-TCP constructs have an overall inhibitory effect on monocyte-derived DC maturation.

摘要

间充质干细胞(MSCs)因其免疫调节和/或免疫抑制特性,不仅在再生医学领域,而且在自身免疫性疾病治疗或器官移植领域都引起了关注。树突状细胞(DCs)通过促进抗原特异性 T 细胞激活,在启动和调节免疫反应中发挥着关键作用。在本研究中,我们研究了种植在β-磷酸三钙(β-TCP)支架上的人颌骨骨膜祖细胞(JPC)对单核细胞来源的 DC 分化的影响。在存在正常(Co)和成骨诱导(Ob)JPC 种植的β-TCP 构建体的情况下,观察到分化的 DC 数量明显减少。基因表达分析显示,在 Ob 条件下,DC 中的白细胞介素-12 亚单位 p35(IL-12p35)和白细胞介素-12 受体β2(IL-12Rβ2)和前炎性细胞因子干扰素-γ(IFN-γ)水平显著降低,而白细胞介素-8(IL-8)基因水平显著升高。此外,在种植有 JPC 的β-TCP 构建体存在的情况下,DC 中的白细胞介素-10(IL-10)基因表达显著增加,尤其是在 Ob 条件下。DC 蛋白水平分析表明,在共培养组中粒细胞集落刺激因子(G-CSF)显著上调。我们的结果表明,未分化和成骨诱导的 JPC 种植的β-TCP 构建体对单核细胞来源的 DC 成熟具有整体抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b56/7355649/93875bbcd86a/biomolecules-10-00887-g001.jpg

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