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Exosomes from conditioned media of bone marrow-derived mesenchymal stem cells promote bone regeneration by enhancing angiogenesis
Open accessAbstract
Growth factors in serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (MSC-CM) are known to be effective in bone regeneration. However, the secretomes in MSC-CM that act as active ingredients for bone regeneration, as well as their mechanisms, remains unclear. Exosomes, components of MSC-CM, provide the recipient cells with genetic information and enhance the recipient cellular paracrine stimulation, which contributes to tissue regeneration. We hypothesized that MSC-CM-derived exosomes (MSC-Exo) promoted bone regeneration, and that angiogenesis was a key step. Here, we prepared an MSC-Exo group, MSC-CM group, and Exo-antiVEGF group (MSC-Exo with angiogenesis inhibitor), and examined the osteogenic and angiogenic potential in MSCs. Furthermore, we used a rat model of calvaria bone defect and implanted each sample to evaluate bone formation weekly, until week 4 after treatment. Results showed that MSC-Exo enhanced cellular migration and osteogenic and angiogenic gene expression in MSCs compared to that in other groups. In vivo, early bone formation by MSC-Exo was also confirmed. Two weeks after implantation, the newly formed bone area was 31.5 ± 6.5% in the MSC-Exo group while those in the control and Exo-antiVEGF groups were 15.4 ± 4.4% and 8.7 ± 1.1%, respectively. Four weeks after implantation, differences in the area between the MSC-Exo group and the Exo-antiVEGF or control groups were further broadened. Histologically, notable accumulation of osteoblast-like cells and vascular endothelial cells was observed in the MSC-Exo group; however, fewer cells were found in the Exo-antiVEGF and control groups. In conclusion, MSC-Exo promoted bone regeneration during early stages, as well as enhanced angiogenesis. Considering the tissue regeneration with transplanted cells and their secretomes, this study suggests that exosomes might play an important role, especially in angiogenesis.
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“osteogenesis is closely related with vascularization due to cell-to-cell communication between vascular endothelial cells and osteoblasts [99].”
From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [99]
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“In fact, osteogenesis is closely related with vascularization due to cell-to-cell communication between vascular endothelial cells and osteoblasts [99].”
Metadata
- Authors
- Takeuchi, R., Katagiri, W., Endo, S., & Kobayashi, T.
- Affiliations
- Niigata University (JP)
- Corresponding author
- Katagiri, Wataru
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-11-21
- Volume
- 14
- Issue
- 11
- Pages
- e0225472
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6872157
- OpenAlex
- W2989744940
- Cited by
- 210
- References
- 54
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 33 · 2023: 32 · 2022: 37 · 2021: 51 · 2020: 16
- FWCI
- 8.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (18K09785)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- exosomes, bone marrow-derived mesenchymal stem cells, conditioned medium, bone regeneration, angiogenesis, VEGF inhibitors, osteogenic differentiation, paracrine signaling, cell transplantation, secretome
- MeSH terms
- Animals, Bone Regeneration, Cell Movement, Cells, Cultured, Disease Models, Animal, Humans, Skull, Culture Media, Conditioned, Neovascularization, Physiologic, Cell Culture Techniques, Paracrine Communication, Angiogenesis Inhibitors, Mesenchymal Stem Cell Transplantation, Cell Proliferation, Rats, Exosomes, Mesenchymal Stem Cells
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