Human perivascular stem cell-derived extracellular vesicles mediate bone repair

The vascular wall is a source of progenitor cells that are able to induce skeletal repair, primarily by paracrine mechanisms. Here, the paracrine role of extracellular vesicles (EVs) in bone healing was investigated. First, purified human perivascular stem cells (PSCs) were observed to induce mitoge...

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Bibliographic Details
Published in:eLife 2019-09, Vol.8
Main Authors: Xu, Jiajia, Wang, Yiyun, Hsu, Ching-Yun, Gao, Yongxing, Meyers, Carolyn Ann, Chang, Leslie, Zhang, Leititia, Broderick, Kristen, Ding, Catherine, Peault, Bruno, Witwer, Kenneth, James, Aaron Watkins
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Biological activity
Blood Vessels - cytology
Bone growth
Bone healing
Bone regeneration
bone repair
bone tissue engineering
CD81 antigen
CD9 antigen
Cell Biology
Cell culture
Cell migration
Cell proliferation
Cells, Cultured
Coculture Techniques
Defects
exosome
Extracellular vesicles
Extracellular Vesicles - metabolism
Flow cytometry
Fractures (Injuries)
Gene expression
Humans
mesenchymal stem cell
Methods
Microscopy
Osteocytes - drug effects
Osteocytes - physiology
Osteogenesis
Osteoprogenitor cells
Paracrine signalling
pericyte
Principal components analysis
Progenitor cells
Proteins
Regeneration
Software
Stem cell transplantation
Stem cells
Stem Cells - metabolism
Stem Cells and Regenerative Medicine
Surgery
Tissue engineering
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Description
Summary:The vascular wall is a source of progenitor cells that are able to induce skeletal repair, primarily by paracrine mechanisms. Here, the paracrine role of extracellular vesicles (EVs) in bone healing was investigated. First, purified human perivascular stem cells (PSCs) were observed to induce mitogenic, pro-migratory, and pro-osteogenic effects on osteoprogenitor cells while in non-contact co-culture via elaboration of EVs. PSC-derived EVs shared mitogenic, pro-migratory, and pro-osteogenic properties of their parent cell. PSC-EV effects were dependent on surface-associated tetraspanins, as demonstrated by EV trypsinization, or neutralizing antibodies for CD9 or CD81. Moreover, shRNA knockdown in recipient cells demonstrated requirement for the CD9/CD81 binding partners IGSF8 and PTGFRN for EV bioactivity. Finally, PSC-EVs stimulated bone repair, and did so via stimulation of skeletal cell proliferation, migration, and osteodifferentiation. In sum, PSC-EVs mediate the same tissue repair effects of perivascular stem cells, and represent an 'off-the-shelf' alternative for bone tissue regeneration.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.48191