PMID- 31482845
OWN - NLM
STAT- MEDLINE
DCOM- 20200214
LR  - 20240420
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 8
DP  - 2019 Sep 4
TI  - Human perivascular stem cell-derived extracellular vesicles mediate bone repair.
LID - 10.7554/eLife.48191 [doi]
LID - e48191
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.
CI  - (c) 2019, Xu et al.
FAU - Xu, Jiajia
AU  - Xu J
AUID- ORCID: 0000-0002-6084-2029
AD  - Department of Pathology, Johns Hopkins University, Baltimore, United States.
FAU - Wang, Yiyun
AU  - Wang Y
AD  - Department of Pathology, Johns Hopkins University, Baltimore, United States.
FAU - Hsu, Ching-Yun
AU  - Hsu CY
AD  - Department of Pathology, Johns Hopkins University, Baltimore, United States.
FAU - Gao, Yongxing
AU  - Gao Y
AD  - Department of Pathology, Johns Hopkins University, Baltimore, United States.
FAU - Meyers, Carolyn Ann
AU  - Meyers CA
AD  - Department of Pathology, Johns Hopkins University, Baltimore, United States.
FAU - Chang, Leslie
AU  - Chang L
AD  - Department of Pathology, Johns Hopkins University, Baltimore, United States.
FAU - Zhang, Leititia
AU  - Zhang L
AD  - Department of Pathology, Johns Hopkins University, Baltimore, United States.
AD  - Department of Oral and Maxillofacial Surgery, School of Stomatology, China 
      Medical University, Shenyang, China.
FAU - Broderick, Kristen
AU  - Broderick K
AD  - Department of Surgery, Johns Hopkins University, Baltimore, United States.
FAU - Ding, Catherine
AU  - Ding C
AD  - Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA, 
      Orthopaedic Hospital, Los Angeles, United States.
FAU - Peault, Bruno
AU  - Peault B
AD  - Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, UCLA, 
      Orthopaedic Hospital, Los Angeles, United States.
AD  - Centre For Cardiovascular Science, University of Edinburgh, Edinburgh, United 
      Kingdom.
AD  - MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United 
      Kingdom.
FAU - Witwer, Kenneth
AU  - Witwer K
AD  - Department of Molecular and Comparative Pathobiology, Johns Hopkins University, 
      Baltimore, United States.
AD  - Department of Neurology, Johns Hopkins University, Baltimore, United States.
FAU - James, Aaron Watkins
AU  - James AW
AUID- ORCID: 0000-0002-2002-622X
AD  - Department of Pathology, Johns Hopkins University, Baltimore, United States.
LA  - eng
SI  - GEO/GSE118961
SI  - GEO/GSE130086
GR  - K08 AR068316/AR/NIAMS NIH HHS/United States
GR  - G1000816/MRC_/Medical Research Council/United Kingdom
GR  - R01 AR070773/AR/NIAMS NIH HHS/United States
GR  - R21 DE027922/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190904
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
SB  - IM
MH  - Blood Vessels/*cytology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Extracellular Vesicles/*metabolism
MH  - Humans
MH  - Osteocytes/*drug effects/*physiology
MH  - *Osteogenesis
MH  - Stem Cells/*metabolism
PMC - PMC6764819
OTO - NOTNLM
OT  - bone repair
OT  - bone tissue engineering
OT  - cell biology
OT  - exosome
OT  - human
OT  - mesenchymal stem cell
OT  - mouse
OT  - osteogenesis
OT  - pericyte
OT  - regenerative medicine
OT  - stem cells
COIS- JX, YW, CH, YG, CM, LC, LZ, KB, CD, KW No competing interests declared, BP is the 
      inventor of perivascular stem cell-related patents held by the UC Regents (Patent 
      No. 20160271186), AJ is a scientific advisory board member for Novadip, LLC
EDAT- 2019/09/05 06:00
MHDA- 2020/02/15 06:00
PMCR- 2019/09/04
CRDT- 2019/09/05 06:00
PHST- 2019/05/03 00:00 [received]
PHST- 2019/09/03 00:00 [accepted]
PHST- 2019/09/05 06:00 [pubmed]
PHST- 2020/02/15 06:00 [medline]
PHST- 2019/09/05 06:00 [entrez]
PHST- 2019/09/04 00:00 [pmc-release]
AID - 48191 [pii]
AID - 10.7554/eLife.48191 [doi]
PST - epublish
SO  - Elife. 2019 Sep 4;8:e48191. doi: 10.7554/eLife.48191.