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Therapeutic efficacy-potentiated and diseased organ-targeting nanovesicles derived from mesenchymal stem cells for spinal cord injury treatment

Cited 140 time in Web of Science Cited 142 time in Scopus
Authors

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

Issue Date
2018-08
Publisher
American Chemical Society
Citation
Nano Letters, Vol.18 No.8, pp.4965-4975
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.
ISSN
1530-6984
URI
https://hdl.handle.net/10371/165844
DOI
https://doi.org/10.1021/acs.nanolett.8b01816
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  • School of Chemical and Biological Engineering
Research Area Chemistry, Materials Science

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