Kim Han Young, Kim Tae Jung, Kang Lami, Kim Young-Ju, Kang Min Kyoung, Kim Jonghoon, Ryu Ju Hee, Hyeon Taeghwan, Yoon Byung-Woo, Ko Sang-Bae, Kim Byung-Soo
Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea; School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
Department of Neurology, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
Biomaterials. 2020 Jun;243:119942. doi: 10.1016/j.biomaterials.2020.119942. Epub 2020 Mar 6.
Exosomes and extracellular nanovesicles (NV) derived from mesenchymal stem cells (MSC) may be used for the treatment of ischemic stroke owing to their multifaceted therapeutic benefits that include the induction of angiogenesis, anti-apoptosis, and anti-inflammation. However, the most serious drawback of using exosomes and NV for ischemic stroke is the poor targeting on the ischemic lesion of brain after systemic administration, thereby yielding a poor therapeutic outcome. In this study, we show that magnetic NV (MNV) derived from iron oxide nanoparticles (IONP)-harboring MSC can drastically improve the ischemic-lesion targeting and the therapeutic outcome. Because IONP stimulated expressions of therapeutic growth factors in the MSC, MNV contained greater amounts of those therapeutic molecules compared to NV derived from naive MSC. Following the systemic injection of MNV into transient middle-cerebral-artery-occlusion (MCAO)-induced rats, the magnetic navigation increased the MNV localization to the ischemic lesion by 5.1 times. The MNV injection and subsequent magnetic navigation promoted the anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion, thereby yielding a considerably decreased infarction volume and improved motor function. Overall, the proposed MNV approach may overcome the major drawback of the conventional MSC-exosome therapy or NV therapy for the treatment of ischemic stroke.
源自间充质干细胞（MSC）的外泌体和细胞外纳米囊泡（NV）因其多方面的治疗益处，包括诱导血管生成、抗凋亡和抗炎作用，可用于治疗缺血性中风。然而，全身给药后，将外泌体和NV用于缺血性中风最严重的缺点是对脑缺血病灶的靶向性差，从而导致治疗效果不佳。在本研究中，我们表明，源自负载氧化铁纳米颗粒（IONP）的MSC的磁性NV（MNV）可显著改善缺血病灶靶向性和治疗效果。由于IONP刺激了MSC中治疗性生长因子的表达，与源自未处理的MSC的NV相比，MNV含有更多量的这些治疗分子。将MNV全身注射到短暂性大脑中动脉闭塞（MCAO）诱导的大鼠体内后，磁性导航使MNV在缺血病灶处的定位增加了5.1倍。MNV注射及随后的磁性导航促进了缺血性脑损伤中的抗炎反应、血管生成和抗凋亡，从而使梗死体积显著减小，运动功能得到改善。总体而言，所提出的MNV方法可能克服传统MSC外泌体疗法或NV疗法治疗缺血性中风的主要缺点。
