Work

Human perivascular stem cell-derived extracellular vesicles mediate bone repair

Year: 2019

Type: article

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.

Source: eLife

DOI: 10.7554/elife.48191

Authors: Jiajia Xu, Yiyun Wang, Ching-Yun Hsu, Yongxing Gao, Carolyn Ann Meyers, Leslie Chang, Leititia Zhang, Kristen Broderick, Catherine Ding, Bruno Peault, Kenneth Witwer, Aaron Watkins James

Institutions: Johns Hopkins University, China Medical University, University of California, Los Angeles, Orthopaedic Hospital, MRC Centre for Regenerative Medicine, University of Edinburgh

Language: English

Topic: Extracellular vesicles in disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500

Funders: U.S. Department of Defense, American Cancer Society, Orthopaedic Research and Education Foundation, Musculoskeletal Transplant Foundation, Maryland Stem Cell Research Fund, National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research

Awards: G1028362368, G1236877285, G241257592, NELL-1 isoforms for the systemic treatment of osteoporosis, G3996890053, G4119534169, G4412696785, DEVELOPMENT OF SMOOTHENED AGONIST NON-PHOSPHOLIPID LIPOSOMAL NANOPARTICLES FOR BONE REPAIR, ENDOGENOUS AND EXOGENOUS PERICYTES IN THE PATHOBIOLOGY AND TREATMENT OF OSTEOARTHRITIS, DKK1 ANTAGONISM FOR STROMAL VASCULAR FRACTION, G5850682332, Role of sensory nerves in cranial bone repair, G7291523422, G7604553565, Direct and indirect contributions of perivascular stem cells to bone healing, G8166743225

OpenAlex ID: W2971554550

FWCI: 4.631

Cites: 83

Cited by: 87

Related to: 10