The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model
Open accessAbstract
Paracrine signaling by bone-marrow-derived mesenchymal stem cells (MSCs) plays a major role in tissue repair. Although the production of regulatory cytokines by MSC transplantation is a critical modulator of tissue regeneration, we focused on exosomes, which are extracellular vesicles that contain proteins and nucleic acids, as a novel additional modulator of cell-to-cell communication and tissue regeneration. To address this, we used radiologic imaging, histological examination, and immunohistochemical analysis to evaluate the role of exosomes isolated from MSC-conditioned medium (CM) in the healing process in a femur fracture model of CD9−/− mice, a strain that is known to produce reduced levels of exosomes. We found that the bone union rate in CD9−/− mice was significantly lower than wild-type mice because of the retardation of callus formation. The retardation of fracture healing in CD9−/− mice was rescued by the injection of exosomes, but this was not the case after the injection of exosomes-free conditioned medium (CM-Exo). The levels of the bone repair-related cytokines, monocyte chemotactic protein-1 (MCP-1), MCP-3, and stromal cell-derived factor-1 in exosomes were low compared with levels in CM and CM-Exo, suggesting that bone repair may be in part mediated by other exosome components, such as microRNAs. These results suggest that exosomes in CM facilitate the acceleration of fracture healing, and we conclude that exosomes are a novel factor of MSC paracrine signaling with an important role in the tissue repair process. Significance: This work focuses on exosomes, which are extracellular vesicles, as a novel additional modulator of cell-to-cell communication. This study evaluated the role of exosomes isolated from mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) in the fracture-healing process of CD9−/− mice, a strain that is known to produce reduced levels of exosomes. Retardation of fracture healing in CD9−/− mice was rescued by the injection of MSC exosomes, but this was not the case after the injection of exosome-free CM. This study finds that MSC exosomes are a novel factor of MSC paracrine signaling, with an important role in the tissue repair process.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Administration of MSCs derived exosomes has been reported to be efficacious in promoting skeletal muscle regeneration [12], cartilage repair [13], and bone fracture healing [14], and cutaneous wound healing [15].”
From A tailored bioactive 3D porous poly(lactic-acid)-exosome scaffold with osteo-immunomodulatory and osteogenic differentiation properties (2022) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., & Wood, M. J. A. (2011) · Nature Biotechnology · doi:10.1038/nbt.1807 · Cited by 4,930
Membrane vesicles as conveyors of immune responses
Théry, C., Ostrowski, M., & Segura, É. (2009) · Nature reviews. Immunology · doi:10.1038/nri2567 · Cited by 3,996
Mesenchymal stem cells as trophic mediators
Caplan, A. I., & Dennis, J. E. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20886 · Cited by 2,992
Exosomes: Extracellular organelles important in intercellular communication
Mathivanan, S., Ji, H. L., & Simpson, R. J. (2010) · Journal of Proteomics · doi:10.1016/j.jprot.2010.06.006 · Cited by 2,581
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
Pan, B., & Johnstone, R. M. (1983) · Cell · doi:10.1016/0092-8674(83)90040-5 · Cited by 2,042
Secretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells
Kosaka, N., Iguchi, H., Yoshioka, Y., Takeshita, F., Matsuki, Y., & Ochiya, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.107821 · Cited by 1,934
Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells
Ohno, S.-I., Takanashi, M., Sudo, K., Ueda, S., Ishikawa, A., Matsuyama, N., Fujita, K., Mizutani, T., Ohgi, T., Ochiya, T., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2012.180 · Cited by 1,666
Mesenchymal Stem Cells and Their Potential as Cardiac Therapeutics
Pittenger, M. F., & Martin, B. J. (2004) · Circulation Research · doi:10.1161/01.res.0000135902.99383.6f · Cited by 1,434
Cited by
Sorted by citations
Concise review: MSC-derived exosomes for cell-free therapy
Phinney, D. G., & Pittenger, M. F. (2017) · Stem Cells · doi:10.1002/stem.2575 · Cited by 1,834
Advances in therapeutic applications of extracellular vesicles
Wiklander, O. P. B., Brennan, M. Á., Lötvall, J., Breakefield, X. O., & EL Andaloussi, S. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav8521 · Cited by 1,039
Han, Y., Yang, J., Fang, J., Zhou, Y., Candi, E., Wang, J., Hua, D., Shao, C., & Shi, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00932-0 · Cited by 720
Clinical applications of stem cell-derived exosomes
Tan, F., Li, X., Wang, Z., Li, J., Shahzad, K., & Zheng, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01704-0 · Cited by 708
Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine
Hade, M. D., Suire, C. N., & Suo, Z. (2021) · Cells · doi:10.3390/cells10081959 · Cited by 642
Metadata
- Authors
- Furuta, T., Miyaki, S., Ishitobi, H., Ogura, T., Kato, Y., Kamei, N., Miyado, K., Higashi, Y., & Ochi, M.
- Affiliations
- Hiroshima University (JP)
- Hiroshima University Hospital (JP)
- National Institute of Advanced Industrial Science and Technology (JP)
- National Center For Child Health and Development (JP)
- Corresponding author
- Furuta, Taisuke
- ORCID
- Venue
- Stem Cells Translational Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-07-26
- Volume
- 5
- Issue
- 12
- Pages
- 1620-1630
- ISSN
- 2157-6564 (ISSN-L)
- 2157-6580
- PMC
- PMC5189643
- OpenAlex
- W2490529699
- Cited by
- 444
- References
- 60
- Citations by year
- 2026: 18 · 2025: 35 · 2024: 41 · 2023: 44 · 2022: 52 · 2021: 90 · 2020: 64 · 2019: 44 · 2018: 37 · 2017: 17 · 2016: 1
- FWCI
- 17.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Stem Cells Translational Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Hiroshima University Acedemic Information Repository (Hiroshima University) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (21249079)
- Japan Society for the Promotion of Science (26293363, 16K21192, 15H04959, 24689057, 14J05729, 21249079, 15H04365)
- 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
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone fractures and treatments
- Keywords
- mesenchymal stem cells, exosomes, fracture healing, paracrine signaling, extracellular vesicles, CD9, conditioned medium, callus formation, bone regeneration, microRNA, CXCL12, MCP-1, tissue regeneration
- MeSH terms
- Animals, Body Weight, Disease Models, Animal, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, Tibia, Bone Density, Cytokines, Culture Media, Conditioned, Fracture Healing, Gene Expression Profiling, MicroRNAs, Cell Line, Tumor, Exosomes, Mesenchymal Stem Cells, Tetraspanin 29
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
