间充质干细胞
脊髓损伤
微泡
再生医学
脊髓
医学
全身给药
干细胞
干细胞疗法
癌症研究
外体
药理学
细胞生物学
病理
化学
体内
生物
小RNA
生物技术
精神科
基因
生物化学
作者
Han Young Kim,Hemant Kumar,Min-Jae Jo,Jong‐Hoon Kim,Jeong‐Kee Yoon,Ju‐Ro Lee,Mikyung Kang,Yeon Woong Choo,Seuk Young Song,Sung Pil Kwon,Taeghwan Hyeon,Inbo Han,Byung Soo Kim
出处
期刊:Nano Letters
[American Chemical Society]
日期:2018-07-11
卷期号:18 (8): 4965-4975
被引量:131
标识
DOI:10.1021/acs.nanolett.8b01816
摘要
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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