Human perivascular stem cell-derived extracellular vesicles mediate bone repair
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 04, 2019
- Source ID
- 10.7554/elife.48191
Entities
People
- Aaron W James
- Bruno Peault
- Carolyn Ann Meyers
- Catherine Ding
- Ching-yun Hsu
- Jiajia Xu
- Kenneth W. Witwer
- Kristen Broderick
- Leititia Zhang
- Leslie Chang
- Yiyun Wang
- Yongxing Gao
Organizations
- American Cancer Society
- China Medical University
- Johns Hopkins University
- Maryland Stem Cell Research Fund
- Musculoskeletal Transplant Foundation
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Dental and Craniofacial Research
- Orthopaedic Research and Education Foundation
- United States Department of Defense
- University of California, Los Angeles
- University of Edinburgh