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

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Title
Therapeutic Efficacy-Potentiated and Diseased Organ-Targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment
Author(s)
Han Young Kim; Hemant Kumar; Min-Jae Jo; Jonghoon Kim; Jeong-Kee Yoon; Ju-Ro Lee; Mikyung Kang; Yeon Woong Choo; Seuk Young Song; Sung pil Kwon; Taeghwan Hyeon; In-Bo Han; Byung-Soo Kim
Publication Date
2018-08
Journal
NANO LETTERS, v.18, no.8, pp.4965 - 4975
Publisher
AMER CHEMICAL SOC
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. © 2018 American Chemical Society
URI
https://pr.ibs.re.kr/handle/8788114/5214
ISSN
1530-6984
Appears in Collections:
Center for Nanoparticle Research(나노입자 연구단) > Journal Papers (저널논문)
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