Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healing
Open accessAbstract
Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healingMesenchymal stem/stromal cells (MSCs) have demonstrated therapeutic efficacy for bone regeneration in animal and clinical studies.Although MSCs were initially thought to differentiate to various cell types to replace the injured/ diseased tissue, it is now accepted that these cells secrete factors to promote tissue repair. 1 Among these factors, small extracellular vesicles (sEVs) of size 50e200 nm, which include the exosomes, have been identified as the principal agent mediating the wide-ranging therapeutic efficacy of MSCs. 2 Several studies have also reported the therapeutic effects of MSC-sEVs to enhance bone repair in animal models, as recently reviewed.3 However, the cellular processes and mechanisms mediated by MSC-sEVs in bone regeneration remain to be fully elucidated.In this study, we employed a rat calvaria defect model to investigate the cellular processes activated by MSC-sEVs during bone repair (Supplementary Methods).Briefly, MSC-sEVs were prepared as previously described, 4 and characterized in accordance with the MISEV2018 guidelines.5 Collagen sponges with 100 mg MSC-sEVs in 100 ml PBS (CS/ sEVs) or equivalent volume of phosphate-buffered saline (PBS, CS/Control) were implanted to 8-mm diameter critical-size calvaria defects surgically created in 32 rats.Another five rats served as age-matched naive control.At 1 and 8 weeks, samples were harvested for analyses using micro-computed tomography (micro-CT), histology and immunohistochemistry.Micro-CT analysis revealed minimal bone formation in both groups at 1 week (Fig. S1).Despite limited bone formation, CS/sEVs group showed better cell infiltration and Peer review under responsibility of Chongqing Medical University.
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MSC-Exos motivate inherent receptor cells rather than directly differentiating into parenchymal cells for tissue repair.
“These MSC-Exos motivate the inherent receptor cells rather than directly differentiating into parenchymal cells for tissue repair [18,19].”
From Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation (2025) · cites this paper as [18]
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- Authors
- Chuah, S. J., Yong, C. W., Teo, K. Y. W., Chew, J. R. J., Cheow, Y. A., Zhang, S., Wong, R. C. W., Lim, A. A. T., Lim, S. K., & Toh, W. S.
- Affiliations
- National University of Singapore (SG)
- Agency for Science, Technology and Research (SG)
- Corresponding author
- Toh, Wei Seong
- ORCID
- Venue
- Genes & Diseases
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 9
- Issue
- 4
- Pages
- 841-844
- ISSN
- 2352-3042 (ISSN-L)
- PMC
- PMC9170598
- OpenAlex
- W4200108680
- Cited by
- 24
- References
- 5
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 2 · 2023: 8 · 2022: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genes & Diseases (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Agency for Science, Technology and Research (H19H6a0026)
- National Medical Research Council (R221000123213)
- National University of Singapore (R221000114114, R221000134114)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- mesenchymal stem cells, small extracellular vesicles, macrophage polarization, bone regeneration, calvarial defect, exosomes, cell infiltration, bone formation
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