Human perivascular stem cell-derived extracellular vesicles mediate bone repair
- Johns Hopkins University, United States
- University of California, Los Angeles, United States
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.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE118961 and GSE130086.
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Expression data from human perivascular stem cell-derived extracellular vesicles (PSC-EVs) and PSCsNCBI Gene Expression Omnibus, GSE130086.
Article and author information
Author details
Aaron Watkins James
Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR070773)
- Aaron Watkins James
Department of Defense (W81XWH-18-10613)
- Aaron Watkins James
National Institute of Dental and Craniofacial Research (R21 DE027922)
- Aaron Watkins James
Department of Defense (W81XWH-18-1-0121)
- Aaron Watkins James
American Cancer Society (Research Scholar Grant RSG-18-027-01-CSM)
- Aaron Watkins James
Orthopaedic Research and Education Foundation with funding provided by the Musculoskeletal Transplant Foundation
- Aaron Watkins James
Maryland Stem Cell Research Foundation
- Aaron Watkins James
Musculoskeletal Transplant Foundation
- Aaron Watkins James
National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08 AR068316)
- Aaron Watkins James
Department of Defense (W81XWH-18-1-0336)
- Aaron Watkins James
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Clifford J Rosen, Maine Medical Center Research Institute, United States
Ethics
Animal experimentation: All animal experiments were performed according to the approved protocol of the Animal Care and Use Committee (ACUC) at Johns Hopkins University (Approval No. MO16M226).
Human subjects: Human lipoaspirate was obtained under IRB approval at JHU with a waiver of informed consent (Approval No. IRB00119905 and IRB00137530).
Version history
- Received: May 3, 2019
- Accepted: September 3, 2019
- Accepted Manuscript published: September 4, 2019 (version 1)
- Version of Record published: September 27, 2019 (version 2)
Copyright
© 2019, Xu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Human perivascular stem cell-derived extracellular vesicles mediate bone repair
eLife 8:e48191.
https://doi.org/10.7554/eLife.48191
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