The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
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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Valadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007) · Nature Cell Biology · doi:10.1038/ncb1596 · Cited by 12,834
Extracellular vesicles: Exosomes, microvesicles, and friends
Raposo, G., & Stoorvogel, W. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201211138 · Cited by 8,099
A perivascular origin for mesenchymal stem cells in multiple human organs
Crisan, M., Yap, S., Casteilla, L., Chen, C.-W., Corselli, M., Park, T. S., Andriolo, G., Sun, B., Zheng, B., Zhang, L., et al. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.07.003 · Cited by 3,991 · cited 1×
“Stem cells are present in various organs and tissues, and they play an important role in maintaining homeostasis in the healthy body [35].”
BackgroundVascular endothelial growth factor (VEGF) and its receptors
Neufeld, G., Cohen, T., Gengrinovitch, S., & Gluzman‐Poltorak, Z. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.1.9 · Cited by 3,511
Basic and Therapeutic Aspects of Angiogenesis
Potente, M., Gerhardt, H., & Carmeliet, P. (2011) · Cell · doi:10.1016/j.cell.2011.08.039 · Cited by 2,771
Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury
Lai, R. C., Arslan, F., Lee, M. M., Sze, N. S. K., Choo, A., Chen, T. S., Salto-Tellez, M., Timmers, L., Lee, C. N., El Oakley, R. M., et al. (2010) · Stem Cell Research · doi:10.1016/j.scr.2009.12.003 · Cited by 2,215
Vascularization in tissue engineering
Rouwkema, J., Rivron, N. C., & van Blitterswijk, C. (2008) · Trends in biotechnology · doi:10.1016/j.tibtech.2008.04.009 · Cited by 1,218
Mesenchymal stem cells: a new trend for cell therapy
Wei, X., Yang, X. F., Han, Z., Qu, F.-F., Shao, L., & Shi, Y. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.50 · Cited by 964
Exosomes Derived from Mesenchymal Stem Cells
Yu, B., Zhang, X., & Li, X. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15034142 · Cited by 788
Zhang, Y., Chopp, M., Meng, Y., Katakowski, M., Xin, H., Mahmood, A., & Xiong, Y. (2015) · Journal of neurosurgery · doi:10.3171/2014.11.jns14770 · Cited by 737
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Mai, T. H., Itoh, S., Kagioka, T., Abe, M., & Hayashi, M. (2026) · Stem Cells International · doi:10.1155/sci/1860064
Craniofacial Fracture and Secretome: A Systematic Review
Oley, M. H., Oley, M. C., Suoth, S. C., Yong, H., Faruk, M., Sukarno, V., & Gunawan, D. F. (2026) · Plastic & Reconstructive Surgery Global Open · doi:10.1097/gox.0000000000007482
Study on Breast Cancer Therapy Using Low-Temperature Plasma Treated L-Arginine Solution
杜, 荔., & DU, L. (2026) · Institutional Repositories DataBase (IRDB)
Mesenchymal stem cells and extracellular vesicles in bone regeneration
Saranya, S. S., Baby, H., & Fernandez, F. B. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45056-3.00018-2
Noh, M., Heo, T.-H., Kang, M.-K., & Jeong, G. (2026) · Polymers · doi:10.3390/polym18141781
Application of Stem Cell-Derived Extracellular Vesicles in Craniomaxillofacial Bone Regeneration
Zhuang, J., Wu, J., Ma, Y., Yin, L., & Wang, Y. (2026) · ACS Applied Bio Materials · doi:10.1021/acsabm.6c00476
Dede, E. Ç., Çam, S. B., Korkusuz, F., Erdem, E., Bakan, F., & Korkusuz, P. (2026) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.70159
Extracellular Vesicles and Their Role in Osteogenesis
Jäger, M., & Sowislok, A. (2026) · Bioengineering · doi:10.3390/bioengineering13091086
Meglei, A. Y., Paymeteva, D., Nedorubova, I. A., Basina, V. P., Goldshtein, D. V., & Bukharova, T. B. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27219486
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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