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The tissue origin effect of extracellular vesicles on cartilage and bone regeneration
Abstract
Direct implantation of mesenchymal stem cells (MSCs) for cartilage and bone tissue engineering faces challenges, such as immune rejection and loss of cellular viability or functionality. As nanoscale natural particles, exosomes or small extracellular vesicles (EVs) of MSCs have potential to circumvent these problems. It is significant to investigate the impact of the tissue origin of MSCs on the therapeutic bioactivity of their corresponding EVs for cartilage and bone regeneration. Here, rat MSCs isolated from the adipose, bone marrow, and synovium are cultured to obtain their corresponding EVs (ADSC-EVs, BMSC-EVs, and SMSC-EVs, respectively). The ADSC-EVs stimulate the migration, proliferation, and chondrogenic and osteogenic differentiation of BMSCs in vitro as well as cartilage and bone regeneration in a mouse model more than the BMSC-EVs or SMSC-EVs. Proteomics analysis reveals that the tissue origin contributes to the distinct protein profiles among the three types of EVs, which induced cartilage and bone regenerative capacities by potential mechanisms of regulating signaling pathways including focal adhesion, ECM-receptor interaction, actin cytoskeleton, cAMP, and PI3K-Akt signaling pathways. Consequently, these findings provide insight that the adipose may be a superior candidate in EV-based nanomedicine for cartilage and bone regeneration. STATEMENT OF SIGNIFICANCE: Extracelluar vesicles (EVs) of mesenchymal stem cells (MSCs) have been considered as a promising approach in cartilage and bone tissue engineering. In this study, for the first time, we investigated the tissue origin effect of EVs on chondrogenesis and osteogenesis of MSCs in vitro and in vivo. The results demonstrated that EVs of adipose-derived MSCs showed the most efficiency. Meanwhile, protein proteomics revealed the potential mechanisms. We provide a novel evidence that the adipose is a superior reservoir in EV-based nanotechnologies and biomaterials for cartilage and bone regeneration.
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“Exosomes secreted by human adipose-derived mesenchymal stem cells (hADSCs-Exos) are reportedly superior in enhancing the efficacy of biomaterials for bone regeneration [13].”
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“Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effective therapeutic tool for repairing bone defects.”
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Metadata
- Authors
- Li, Q., Yu, H., Sun, M., Yang, P., Hu, X., Ao, Y., & Cheng, J.
- Affiliations
- Peking University (CN)
- Corresponding author
- Ao, Yingfang
- Cheng, Jin
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2021-04
- Volume
- 125
- Pages
- 253-266
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W3134379672
- Cited by
- 172
- References
- 68
- Citations by year
- 2026: 12 · 2025: 30 · 2024: 61 · 2023: 31 · 2022: 27 · 2021: 11
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Beijing Municipal Science and Technology Commission
- National Natural Science Foundation of China
- Beijing Natural Science Foundation
- 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 › Dentistry › Periodontics › Periodontal Regeneration and Treatments
- Keywords
- extracellular vesicles, mesenchymal stem cells, tissue of origin, cartilage regeneration, bone regeneration, adipose-derived stem cells, bone marrow-derived stem cells, synovial stem cells, chondrogenic differentiation, osteogenic differentiation, EV proteomics, signaling pathways
- MeSH terms
- Extracellular Vesicles, Animals, Bone Regeneration, Cartilage, Cell Differentiation, Osteogenesis, Phosphatidylinositol 3-Kinases, Chondrogenesis, Mice, Rats
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