Application of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Stroke: Biodistribution and MicroRNA Study
Abstract
Mesenchymal stem cells (MSCs) exert their therapeutic capability through a variety of bioactive substances, including trophic factors, microRNAs, and extracellular vesicles (EVs) in infarcted tissues. We therefore hypothesized that MSC-derived EVs (MSC-EVs) possess therapeutic molecules similar to MSCs. Moreover, given their nature as nanosized and lipid-shielded particles, the intravenous infusion of MSC-EVs would be advantageous over MSCs as a safer therapeutic approach. In this study, we investigated the biodistribution, therapeutic efficacy, and mode of action of MSC-EVs in a rat stroke model. MSC-EVs successfully stimulated neurogenesis and angiogenesis in vivo. When compared to the MSC-treated group, rats treated with MSC-EVs exhibited greater behavioral improvements than the control group (p < 0.05). Our biodistribution study using fluorescence-labeled MSC-EVs and MSCs demonstrated that the amounts of MSC-EVs in the infarcted hemisphere increased in a dose-dependent manner, and were rarely found in the lung and liver. In addition, MSC-EVs were highly inclusive of various proteins and microRNAs (miRNAs) associated with neurogenesis and/or angiogenesis compared to fibro-EVs. We further analyzed those miRNAs and found that miRNA-184 and miRNA-210 were essential for promoting neurogenesis and angiogenesis of MSC-EVs, respectively. MSC-EVs represent an ideal alternative to MSCs for stroke treatment, with similar medicinal capacity but an improved safety profile that overcomes cell-associated limitations in stem cell therapy.
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MSC-derived exosomes can successfully stimulate neurogenesis and angiogenesis in a rat stroke model.
“The results illustrated strong evidence for MSC-derived exosomes could successfully stimulate neurogenesis and angiogenesis in that model [69].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [69]
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- Authors
- Moon, G. J., Sung, J. H., Kim, D. H., Kim, E. H., Cho, Y. H., Son, J. P., Cha, J. M., & Bang, O. Y.
- Affiliations
- Kyungpook National University (KR)
- Samsung Medical Center (KR)
- Sungkyunkwan University (KR)
- Incheon National University (KR)
- Corresponding author
- Bang, Oh Young
- ORCID
- Venue
- Translational Stroke Research
- Published
- 2018-10-19
- Volume
- 10
- Issue
- 5
- Pages
- 509-521
- ISSN
- 1868-4483 (ISSN-L)
- 1868-601X
- OpenAlex
- W2897643946
- Cited by
- 166
- References
- 49
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 24 · 2023: 32 · 2022: 28 · 2021: 28 · 2020: 21 · 2019: 4 · 2018: 1
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Translational Stroke Research (publishedVersion)
- PubMed (publishedVersion)
- 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 › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- mesenchymal stem cell-derived extracellular vesicles, stroke, tissue distribution, microRNA, miR-210, neurogenesis, angiogenesis, rat stroke model, functional recovery
- MeSH terms
- Extracellular Vesicles, Animals, Brain, Disease Models, Animal, Male, Rats, Sprague-Dawley, Stroke, MicroRNAs, Angiogenesis Inducing Agents, Mesenchymal Stem Cell Transplantation, Neurogenesis, Mesenchymal Stem Cells
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