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 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.
eLife