Therapeutic Efficacy-Potentiated and Diseased Organ-Targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment
- 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
- Aug-2018
- Publisher
- AMER CHEMICAL SOC
- Keywords
- Exosomes; iron oxide nanoparticles; mesenchymal stem cells; nanovesicles; spinal cord injury
- Citation
- NANO LETTERS, v.18, no.8, pp 4965 - 4975
- Pages
- 11
- Journal Title
- NANO LETTERS
- Volume
- 18
- Number
- 8
- Start Page
- 4965
- End Page
- 4975
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/70020
- DOI
- 10.1021/acs.nanolett.8b01816
- ISSN
- 1530-6984
1530-6992
- 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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Collections - College of Biotechnology & Natural Resource > Department of Systems Biotechnology > 1. Journal Articles
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