TY - JOUR
T1 - 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
N1 - Publisher Copyright:
© Xu et al.
PY - 2019/9
Y1 - 2019/9
N2 - 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.
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.
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U2 - 10.7554/eLife.48191
DO - 10.7554/eLife.48191
M3 - Article
C2 - 31482845
AN - SCOPUS:85072848515
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e48191
ER -