Therapeutic Efficacy-Potentiated and Diseased Organ-Targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment
Abstract
Human mesenchymal stem cell (hMSC)-derived exosomes have been spotlighted as a promising therapeutic agent for cell-free regenerative medicine. However, poor organ-targeting ability and insufficient therapeutic efficacy of systemically injected hMSC-exosomes were identified as critical limitations for their further applications. Therefore, in this study we fabricated iron oxide nanoparticle (IONP)-incorporated exosome-mimetic nanovesicles (NV-IONP) from IONP-treated hMSCs and evaluated their therapeutic efficacy in a clinically relevant model for spinal cord injury. Compared to exosome-mimetic nanovesicles (NV) prepared from untreated hMSCs, NV-IONP not only contained IONPs which act as a magnet-guided navigation tool but also carried greater amounts of therapeutic growth factors that can be delivered to the target cells. The increased amounts of therapeutic growth factors inside NV-IONP were attributed to IONPs that are slowly ionized to iron ions which activate the JNK and c-Jun signaling cascades in hMSCs. In vivo systemic injection of NV-IONP with magnetic guidance significantly increased the amount of NV-IONP accumulating in the injured spinal cord. Accumulated NV-IONP enhanced blood vessel formation, attenuated inflammation and apoptosis in the injured spinal cord, and consequently improved spinal cord function. Taken together, these findings highlight the development of therapeutic efficacy-potentiated extracellular nanovesicles and demonstrate their feasibility for repairing injured spinal cord.
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In a clinically relevant SCI model, systemic delivery of IONP-incorporated exosome-mimetic nanovesicles (NV-IONP) directed by magnetic targeting significantly increased accumulation at the lesion site.
“In a clinically relevant model of SCI, the systemic delivery of NV-IONP, directed by magnetic targeting, significantly increased their accumulation at the lesion site.”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [295]
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- Authors
- Kim, H. Y., Kumar, H., Jo, M.-J., Kim, J., Yoon, J.-K., Lee, J.-R., Kang, M., Choo, Y. W., Song, S. Y., Kwon, S. P., Hyeon, T., Han, I.-B., & Kim, B.-S.
- Affiliations
- Seoul National University (KR)
- CHA University Bundang Medical Center (KR)
- Department of Neurosurgery, CHA University, CHA Bundang Medical Center, Seongnam-si, 13488, Republic of Korea
- Corresponding author
- Kim, Byung-Soo
- ORCID
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-07-11
- Volume
- 18
- Issue
- 8
- Pages
- 4965-4975
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- OpenAlex
- W2825453881
- Cited by
- 190
- References
- 44
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 32 · 2023: 27 · 2022: 34 · 2021: 37 · 2020: 23 · 2019: 9 · 2018: 3
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Korea Health Industry Development Institute (HI18C0183)
- National Research Foundation of Korea (2017R1A2B3005842, 2017R1C1B1011397)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- mesenchymal stem cell-derived exosomes, iron oxide nanoparticles, magnetic targeting, spinal cord injury, JNK/c-Jun signaling, iron release, growth factor delivery, angiogenesis, neuroinflammation, apoptosis
- MeSH terms
- Animals, Drug Carriers, Humans, Spinal Cord Injuries, Signal Transduction, PC12 Cells, Apoptosis, Neovascularization, Physiologic, Intercellular Signaling Peptides and Proteins, Biomimetic Materials, Mice, Rats, Exosomes, Magnetite Nanoparticles, Mesenchymal Stem Cells, Drug Liberation
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