Extracellular vesicles secreted by dendritic cells can recruit mesenchymal stem/stromal cells: in vitro and ex vivo evidence

Background: Mesenchymal stem/stromal cells (MSC) are being studied for bone regenerative therapies (1). They are likely recruited to lesion sites by activated immune cells, which secrete chemoattractants and extracellular vesicles (EV). We previously showed that human monocyte-derived dendritic cell...

Full description

Saved in:
Bibliographic Details
Published inJournal of extracellular vesicles Vol. 7; pp. 210 - 211
Main Authors Silva, Andreia M, Teixeira, José H, Ferreira, Ana R, Almeida, Maria I, Cunha, Carla, Vasconcelos, Daniela P, Neves, Nuno, Barbosa, Mário A, Santos, Susana G
Format Journal Article
LanguageEnglish
Published Abingdon John Wiley & Sons, Inc 01.01.2018
Subjects
Bone marrow
Chemotactic factors
Dendritic cells
Extracellular vesicles
Femur
Leukocyte migration
Matrix metalloproteinase
Mesenchyme
Metalloproteinase
Monocyte chemoattractant protein 1
Monocytes
Osteopontin
Paracrine signalling
Recruitment
Stromal cells
Tissue inhibitor of metalloproteinase 1
Portugal
Online AccessGet full text

Cover

More Information
Summary:Background: Mesenchymal stem/stromal cells (MSC) are being studied for bone regenerative therapies (1). They are likely recruited to lesion sites by activated immune cells, which secrete chemoattractants and extracellular vesicles (EV). We previously showed that human monocyte-derived dendritic cells (hDC) could recruit MSC via paracrine action (2). Here, we hypothesize that EV secreted by DC would be main effectors of MSC recruitment and that bone injury would influence DC-EV functionality. Methods: EV were isolated from cultures of hDC (hDC-EV) and rat bone marrow (BM)-derived DC (rDC-EV). BM was isolated from an in vivo femoral bone defect model, at 3 and 14 days post-injury. EV effect on primary BM-MSC migration was tested by transwell migration assay. EV chemokine profile was analysed by membrane array. Results: The results obtained show that hDC-EV significantly and dosedependently promoted human MSC recruitment. EV content analysis revealed the presence ofchemotactic mediators, with osteopontin and matrix metalloproteinase-9 being confirmed inside EV. Also, rDC-EV from 14 days post-injury significantly promoted rat MSC migration, compared to those from non-operated animals, whereas rDC-EV from 3 days post-injury significantly decreased it. Of note, rDC-EV from 14 days post-injury were enriched in MCP-1, whereas rDC-EV from 3 days post-injurywere enriched in TIMP-1. Summary/Conclusion: In conclusion, DC-EV can contribute to MSC recruitment, in a dose and time post-injury dependent fashion. These results will be further exploited for development of new bone tissue regenerative strategies.
ISSN:2001-3078