Using Extracellular Vesicles Released by GDNF-Transfected Macrophages for Therapy of Parkinson Disease.
Using Extracellular Vesicles Released by GDNF-Transfected Macrophages for Therapy of Parkinson Disease.
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细胞外囊泡（EVs）是细胞衍生的纳米颗粒，促进蛋白质、脂质和遗传物质的运输，在细胞内通讯中发挥重要作用。作为无毒和非免疫原性的纳米载体，它们具有显著的潜力，可以将药物输送到无法到达的器官和组织，特别是中枢神经系统（CNS）。在此，我们开发了一个基于巨噬细胞来源的ev治疗帕金森病（PD）的新平台。具体来说，我们评估了自体巨噬细胞分泌的EVs的治疗潜力，这些EVs被体外转染以表达胶质细胞系来源的神经营养因子（GDNF）。从转染GDNF的巨噬细胞的条件培养基中收集EV-GDNF，并对GDNF的含量、大小、电荷和ev特异性蛋白的表达进行表征。数据显示，预转染巨噬细胞释放的ev与编码的神经营养因子一起携带编码gdnf的DNA。四个月大的转基因Parkin Q311(X)A小鼠经鼻灌胃给予EV-GDNF治疗，并在一年内评估这种治疗干预对运动功能的影响。在接受EV-GDNF治疗的PD小鼠中，活动能力显著改善，神经元存活增加，神经炎症减少。未检测到EV-GDNF给药引起的体外毒性。总的来说，以ev为基础的方法可以为PD提供多功能和有效的治疗干预。
Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids, and genetic material, playing important roles in intracellular communication. They have remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage-derived EVs to treat Parkinson disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfected ex vivo to express glial-cell-line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that, along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four-month-old transgenic Parkin Q311(X)A mice were treated with EV-GDNF via intranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increases in neuronal survival, and decreases in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administration was detected. Overall, an EV-based approach can provide a versatile and potent therapeutic intervention for PD.
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DOI：
10.1038/mt.2008.1
发表时间：
2008-04
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Dai S;Wei D;Wu Z;Zhou X;Wei X;Huang H;Li G
通讯作者：
Li G
DOI：
10.1016/j.jconrel.2015.07.030
发表时间：
2015-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Batrakova EV;Kim MS
通讯作者：
Kim MS
影响因子：
2.6
作者：
Banks WA
通讯作者：
Banks WA
外泌体作为帕金森氏病疗法的药物。
DOI：
10.1016/j.jconrel.2015.03.033
发表时间：
2015-06-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Haney MJ;Klyachko NL;Zhao Y;Gupta R;Plotnikova EG;He Z;Patel T;Piroyan A;Sokolsky M;Kabanov AV;Batrakova EV
通讯作者：
Batrakova EV
影响因子：
3.4
作者：
Kameda, M.;Shingo, T.;Date, I.
通讯作者：
Date, I.