AI Article Synopsis
- - The vascular wall contains progenitor cells that support skeletal repair through paracrine signaling, primarily using extracellular vesicles (EVs) from perivascular stem cells (PSCs).
- - PSC-derived EVs promote growth, migration, and differentiation of osteoprogenitor cells, with their activity linked to specific proteins (CD9 and CD81) on their surface and partners involved in signaling.
- - The EVs from PSCs not only replicate the repairing effects of the stem cells themselves but also present a practical method for enhancing bone healing in clinical settings.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764819 | PMC |
| http://dx.doi.org/10.7554/eLife.48191 | DOI Listing |
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