TY - JOUR TI - Human perivascular stem cell-derived extracellular vesicles mediate bone repair AU - Xu, Jiajia AU - Wang, Yiyun AU - Hsu, Ching-Yun AU - Gao, Yongxing AU - Meyers, Carolyn Ann AU - Chang, Leslie AU - Zhang, Leititia AU - Broderick, Kristen AU - Ding, Catherine AU - Peault, Bruno AU - Witwer, Kenneth AU - James, Aaron Watkins A2 - Rosen, Clifford J A2 - Banerjee, Utpal A2 - al-Jallad, Hadil VL - 8 PY - 2019 DA - 2019/09/04 SP - e48191 C1 - eLife 2019;8:e48191 DO - 10.7554/eLife.48191 UR - https://doi.org/10.7554/eLife.48191 AB - 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. KW - pericyte KW - mesenchymal stem cell KW - exosome KW - osteogenesis KW - bone tissue engineering KW - bone repair JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -