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Sci Rep. 2017 Mar 6;7:43923. doi: 10.1038/srep43923.

Effect of age on pro-inflammatory miRNAs contained in mesenchymal stem cell-derived extracellular vesicles.

Author information

1
Grupo de Terapia Celular y Medicina Regenerativa (TCMR-CHUAC). CIBER-BBN/ISCIII. Servicio de Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade de A Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
2
Grupo Fisiopatología Endocrina, Nutricional y Médica (FENM-CHUAC), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), SERGAS, Departamento de Medicina, Facultade de Oza, Universidade de A Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
3
Cardiology Department, Health in Code, As Xubias, 15006, A Coruña, Spain.
4
Experimental Rheumatology, Radboudumc University Medical Center, Huispost 272, route 272, Postbus 9101, 6500 HB Nijmegen, The Netherlands.

Abstract

Stem cells possess significant age-dependent differences in their immune-response profile. These differences were analysed by Next-Generation Sequencing of six age groups from bone marrow mesenchymal stem cells. A total of 9,628 genes presenting differential expression between age groups were grouped into metabolic pathways. We focused our research on young, pre-pubertal and adult groups, which presented the highest amount of differentially expressed genes related to inflammation mediated by chemokine and cytokine signalling pathways compared with the newborn group, which was used as a control. Extracellular vesicles extracted from each group were characterized by nanoparticle tracking and flow cytometry analysis, and several micro-RNAs were verified by quantitative real-time polymerase chain reaction because of their relationship with the pathway of interest. Since miR-21-5p showed the highest statistically significant expression in extracellular vesicles from mesenchymal stem cells of the pre-pubertal group, we conducted a functional experiment inhibiting its expression and investigating the modulation of Toll-Like Receptor 4 and their link to damage-associated molecular patterns. Together, these results indicate for the first time that mesenchymal stem cell-derived extracellular vesicles have significant age-dependent differences in their immune profiles.

PMID:
28262816
PMCID:
PMC5338265
DOI:
10.1038/srep43923
[Indexed for MEDLINE]
Free PMC Article

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