Human perivascular stem cell-derived extracellular vesicles mediate bone repair.
Jiajia XuYiyun WangChing-Yun HsuYongxing GaoCarolyn Ann MeyersLeslie ChangLeititia ZhangKristen BroderickCatherine DingBruno PeaultKenneth WitwerAaron Watkins JamesPublished in: eLife (2019)
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.
Keyphrases
- stem cells
- bone mineral density
- induced apoptosis
- endothelial cells
- cell therapy
- cell proliferation
- anti inflammatory
- bone loss
- soft tissue
- mesenchymal stem cells
- cell cycle arrest
- bone regeneration
- bone marrow
- pluripotent stem cells
- induced pluripotent stem cells
- cell death
- body composition
- cell cycle
- mass spectrometry
- dna binding
- high resolution
- signaling pathway
- dengue virus
- men who have sex with men
- high speed