Exosomal miR-423-5p mediates the proangiogenic activity of human adipose-derived stem cells by targeting Sufu
Open accessAbstract
BACKGROUND: Human adipose-derived stem cells (hADSCs) are an important source of cells for regenerative medicine. Evidence of extensive interactions with the surrounding microenvironment has led researchers to focus more on hADSCs as activating agents of regenerative pathways, rather than simply replacing damaged cells. Several studies have found that functional miRNAs can be packaged into exosomes and transferred from donor cells into recipient cells, indicating that transported miRNAs may be a new class of cell-to-cell regulatory species. The aim of the present study was to evaluate whether the exosome-derived miRNAs secreted by hADSCs are capable of influencing angiogenesis, a key step in tissue regeneration. METHODS: Exosomes were purified from hADSCs followed by the characterization of their phenotype and angiogenic potential in vitro. RNA sequencing was performed to detect the miRNAs that were enriched in the hADSC-derived exosomes. A miRNA-mimic experiment was used to detect the key miRNAs in the proangiogenic activity of hADSC-derived exosomes. RESULTS: Exosomes isolated from hADSCs were characterized as round membrane vesicles with a size of approximately 100 nm and were positive for CD9 and flotillin. The exosomes were internalized by primary human umbilical vein endothelial cells (HUVECs) and stimulated HUVEC proliferation and migration. Remarkably, the exosomes promoted vessel-like formation by HUVECs in a dose-dependent manner, and their maximum activity (10 μg/mL) was comparable with that of 5% FBS. The RNA-seq bioinformatics analysis predicted 1119 gene targets of the top 30 exosomal miRNAs in Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and the pathway involved in the angiogenesis was among the top KEGG pathways. Moreover, intact miR-423-5p was further demonstrated to be transferred into HUVECs via exosomes and to exert its angiogenic function by targeting Sufu. CONCLUSIONS: Exosomal miR-423-5p mediated the proangiogenic activity of hADSCs by targeting Sufu, which may contribute to the exploitation of exosomes from hADSCs as a therapeutic tool for regenerative medicine.
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hADSCs-derived exosomes have pro-angiogenic effects.
“Based on these characteristics, and previous studies [16,17] reporting the pro-angiogenic effects of hADSCs-derived exosomes, these reagents appear to be ideal osteoinductive factors in “cell-free” tissue engineering strategies.”
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- Authors
- Xu, F., Xiang, Q., Huang, J., Chen, Q., Yu, N., Long, X., & Zhou, Z.
- Affiliations
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Peking Union Medical College Hospital (CN)
- Corresponding author
- Long, Xiao
- Zhou, Zhou
- Venue
- Stem Cell Research & Therapy
- Published
- 2019-03-21
- Volume
- 10
- Issue
- 1
- Pages
- 106-106
- ISSN
- 1757-6512 (ISSN-L)
- PMC
- PMC6429803
- OpenAlex
- W2937007013
- Cited by
- 60
- References
- 37
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 14 · 2023: 8 · 2022: 10 · 2021: 8 · 2020: 6
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Research & Therapy (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)
- Funders
- National Natural Science Foundation of China (81670444, 81470487, 81870229)
- Beijing University of Chemical Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- exosomes, miR-423-5p, human adipose-derived stem cells, SUFU, angiogenesis, exosomal microRNAs, endothelial cell proliferation and migration, cell-to-cell communication, regenerative medicine
- MeSH terms
- Adipose Tissue, Humans, Repressor Proteins, Stem Cells, Neovascularization, Physiologic, MicroRNAs, Cell Proliferation, Exosomes, Human Umbilical Vein Endothelial Cells
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