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

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Therapeutic Efficacy-Potentiated and Diseased Organ-Targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment
Nano Letters ( IF 9.6 ) Pub Date : 2018-07-11 00:00:00 , DOI: 10.1021/acs.nanolett.8b01816
Han Young Kim ₁ , Hemant Kumar ₂ , Min-Jae Jo ₂ , Jonghoon Kim _{1,

3} , Jeong-Kee Yoon ₁ , Ju-Ro Lee ₁ , Mikyung Kang ₄ , Yeon Woong Choo ₁ , Seuk Young Song ₁ , Sung Pil Kwon ₁ , Taeghwan Hyeon _{1,

3} , In-Bo Han ₂ , Byung-Soo Kim _{1,

4,

5}

Affiliation

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.

中文翻译：

骨髓间充质干细胞衍生的治疗功效强化和病变器官靶向纳米囊泡。

人间充质干细胞（hMSC）衍生的外泌体已被聚焦为一种无细胞再生医学的有前途的治疗剂。然而，全身注射的hMSC-外泌体的器官靶向能力差和治疗功效不足被认为是其进一步应用的关键限制。因此，在这项研究中，我们从IONP治疗的hMSC中制备了掺入氧化铁纳米颗粒（IONP）的模拟外泌体纳米囊泡（NV-IONP），并在临床相关的脊髓损伤模型中评估了它们的治疗效果。与从未经处理的hMSC制备的模拟外泌体的纳米囊泡（NV）相比，NV-IONP不仅包含IONP，它们可作为磁铁引导的导航工具，而且还携带大量可递送至靶细胞的治疗性生长因子。NV-IONP内部治疗性生长因子数量的增加归因于IONP，这些IONP缓慢离子化为铁离子，从而激活hMSC中的JNK和c-Jun信号级联。体内应用磁性引导的NV-IONP全身注射显着增加了受损脊髓中累积的NV-IONP量。累积的NV-IONP增强了血管的形成，减轻了受损脊髓的炎症和细胞凋亡，从而改善了脊髓功能。综上所述，这些发现突出了增强治疗功效的细胞外纳米囊泡的发展，并证明了其修复受损脊髓的可行性。体内应用磁性引导的NV-IONP全身注射显着增加了受损脊髓中累积的NV-IONP量。累积的NV-IONP增强了血管的形成，减轻了受损脊髓的炎症和细胞凋亡，从而改善了脊髓功能。综上所述，这些发现突出了增强治疗功效的细胞外纳米囊泡的发展，并证明了其修复受损脊髓的可行性。体内应用磁性引导的NV-IONP全身注射显着增加了受损脊髓中累积的NV-IONP量。累积的NV-IONP增强了血管的形成，减轻了受损脊髓的炎症和细胞凋亡，从而改善了脊髓功能。综上所述，这些发现突出了增强治疗功效的细胞外纳米囊泡的发展，并证明了其修复受损脊髓的可行性。

更新日期：2018-07-11

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