Cited by 190Extracellular vesicles in diseaseSpinal Cord Injury ResearchNanoparticle-Based Drug Delivery

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Therapeutic Efficacy-Potentiated and Diseased Organ-Targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment

Kim, Han Young, Kumar, Hemant, Jo, Min-Jae, Kim, Jonghoon, Yoon, Jeong-Kee, Lee, Ju-Ro, Kang, Mikyung, Choo, Yeon Woong, Song, Seuk Young, Kwon, Sung Pil, Hyeon, Taeghwan, Han, In-Bo, Kim, Byung-Soo·2018·Nano Letters

DOI 10.1021/acs.nanolett.8b01816

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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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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: Kim, Han Young
Kumar, Hemant
Jo, Min-Jae
Kim, Jonghoon
Yoon, Jeong-Kee
Lee, Ju-Ro
Kang, Mikyung
Choo, Yeon Woong
Song, Seuk Young
Kwon, Sung Pil
Hyeon, Taeghwan
Kim, Byung-Soo
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
DOI: 10.1021/acs.nanolett.8b01816
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 › Clinical Neurology › 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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Therapeutic Efficacy-Potentiated and Diseased Organ-Targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment

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