Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis
Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis
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分化间充质基质细胞衍生的外泌体对炎症和成骨的免疫调节作用
DOI：
10.1002/term.2947
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发表时间：
2019-08-07
影响因子：
3.3
通讯作者：
Zhou, Yinghong
中科院分区：
文献类型：
--
作者：
Wei, Fei;Li, Zhengmao;Zhou, Yinghong
骨髓间充质干/基质细胞（BMSCs）可分化为成骨细胞，在骨再生中发挥重要作用。外泌体是天然的细胞分泌的纳米囊泡，并且最近被降级为生理和病理条件下的细胞通讯的新兴介质。本研究旨在研究复杂的细胞通讯，特别是分化中的BMSCs、免疫细胞（例如，巨噬细胞）和通过外泌体介导的途径新募集的BMSC。首先在各个阶段（分别为第0天、第3天、第7天和第14天）从成骨分化的BMSC中分离外泌体。在巨噬细胞和人BMSC（hBMSC）中检查分离的外来体的细胞摄取。在各种成骨分化阶段（0 d-exo、3d-exo、7 d-exo和14 d-exo）收集的外泌体对hBMSC的活力没有影响。外泌体（0 d-exo、3d-exo和7 d-exo）的摄取显著降低了促炎基因表达和M1表型标记物的水平。我们的结果显示，3d-exo，7 d-exo和14 d-exo导致间充质干细胞/基质细胞迁移的显着增加。此外，0 d-exo显著促进早期成骨标志物的表达，如碱性磷酸酶和骨形态发生蛋白2，表明hBMSC衍生的外泌体的促成骨作用。总的来说，这些结果表明，来源于分化间充质干细胞/基质细胞的外泌体在骨动力学的调节中发挥独特的骨免疫调节作用。
Bone marrow-derived mesenchymal stem/stromal cells (BMSCs) can differentiate into bone-forming osteoblasts, playing a crucial role in bone regeneration. Exosomes are naturally cell-secreted nanovesicles and are lately regraded as an emerging mediator of cellular communication in physiological and pathological conditions. The present study aimed at investigating the complex cellular communications, especially those among the differentiating BMSCs, immune cells (e.g., macrophages), and newly recruited BMSCs via exosome-mediated pathways. Exosomes were first isolated from osteogenically differentiating BMSCs at various stages (Day 0, Day 3, Day 7, and Day 14, respectively). The cellular uptake of isolated exosomes was examined in macrophages and human BMSCs (hBMSCs). The exosomes collected at various osteogenic differentiation stages (0d-exo, 3d-exo, 7d-exo, and 14d-exo) had no effect on the viability of hBMSCs. The uptake of exosomes (0d-exo, 3d-exo, and 7d-exo) significantly decreased proinflammatory-gene expression and the level of an M1 phenotypic marker. Our results then revealed that 3d-exo, 7d-exo, and 14d-exo led to a remarkable increase in mesenchymal stem/stromal cell migration. In addition, 0d-exo significantly promoted the expression of early osteogenic markers, such as alkaline phosphatase and bone morphogenetic protein 2, indicating a pro-osteogenic role of hBMSC-derived exosomes. Collectively, these results suggest that exosomes derived from differentiating mesenchymal stem/stromal cells play a unique osteoimmunomodulatory role in the regulation of bone dynamics.