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树突状细胞衍生的细胞外囊泡介导间充质干细胞/基质细胞的募集。

Dendritic Cell-derived Extracellular Vesicles mediate Mesenchymal Stem/Stromal Cell recruitment.

机构信息

i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal.

INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.

出版信息

Sci Rep. 2017 May 10;7(1):1667. doi: 10.1038/s41598-017-01809-x.

DOI:10.1038/s41598-017-01809-x
PMID:28490808
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5431789/
Abstract

Orchestration of bone repair processes requires crosstalk between different cell populations, including immune cells and mesenchymal stem/stromal cells (MSC). Extracellular vesicles (EV) as mediators of these interactions remain vastly unexplored. Here, we aimed to determine the mechanism of MSC recruitment by Dendritic Cells (DC), hypothesising that it would be mediated by EV. Primary human DC-secreted EV (DC-EV), isolated by ultracentrifugation, were characterized for their size, morphology and protein markers, indicating an enrichment in exosomes. DC-EV were readily internalized by human bone marrow-derived MSC, without impacting significantly their proliferation or influencing their osteogenic/chondrogenic differentiation. Importantly, DC-EV significantly and dose-dependently promoted MSC recruitment across a transwell system and enhanced MSC migration in a microfluidic chemotaxis assay. DC-EV content was analysed by chemokine array, indicating the presence of chemotactic mediators. Osteopontin and matrix metalloproteinase-9 were confirmed inside EV. In summary, DC-EV are naturally loaded with chemoattractants and can contribute to cell recruitment, thus inspiring the development of new tissue regeneration strategies.

摘要

骨修复过程的调控需要不同细胞群体（包括免疫细胞和间充质干细胞（MSC））之间的串扰。细胞外囊泡（EV）作为这些相互作用的介质，仍在广泛探索之中。在这里，我们旨在确定树突状细胞（DC）募集 MSC 的机制，假设它将由 EV 介导。通过超速离心分离得到的原代人 DC 分泌的 EV（DC-EV），其大小、形态和蛋白标志物进行了表征，表明其富含外泌体。DC-EV 可被人骨髓来源的 MSC 轻易内化，而不会显著影响其增殖或影响其成骨/软骨分化。重要的是，DC-EV 可显著且剂量依赖性地促进跨孔系统中 MSC 的募集，并增强 MSC 在微流控趋化性测定中的迁移。通过趋化因子阵列分析了 DC-EV 的内容物，表明存在趋化性介质。骨桥蛋白和基质金属蛋白酶-9 被确认为 EV 内的物质。总之，DC-EV 天然携带趋化因子，可促进细胞募集，从而激发新的组织再生策略的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/9108228b91a0/41598_2017_1809_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/adbd81d4ec6d/41598_2017_1809_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/8a76cc0a00aa/41598_2017_1809_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/700f60aad74c/41598_2017_1809_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/c9fc523ab465/41598_2017_1809_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/8c056bfa916a/41598_2017_1809_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/9108228b91a0/41598_2017_1809_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/adbd81d4ec6d/41598_2017_1809_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/8a76cc0a00aa/41598_2017_1809_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/700f60aad74c/41598_2017_1809_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/c9fc523ab465/41598_2017_1809_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/8c056bfa916a/41598_2017_1809_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8938/5431789/9108228b91a0/41598_2017_1809_Fig6_HTML.jpg

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