Cell-Free Extracellular Vesicles Derived from Human Bone Marrow Endothelial Progenitor Cells as Potential Therapeutics for Microvascular Endothelium Restoration in ALS.
Cell-Free Extracellular Vesicles Derived from Human Bone Marrow Endothelial Progenitor Cells as Potential Therapeutics for Microvascular Endothelium Restoration in ALS.
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DOI：
10.1007/s12017-020-08607-1
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发表时间：
2020-12
影响因子：
3.5
通讯作者：
Borlongan CV
中科院分区：
文献类型：
--
作者：
Garbuzova-Davis S;Willing AE;Ehrhart J;Wang L;Sanberg PR;Borlongan CV
修复肌萎缩侧索硬化症（ALS）中受损的血液-CNS屏障对于防止导致运动神经元功能障碍的有害血液传播因子的进入是必要的。最近，我们发现人骨髓内皮祖细胞（hBM-EPC）移植到症状性ALS小鼠的屏障恢复的好处，通过取代受损的内皮细胞（EC）。此外，移植的细胞可以通过分泌血管生成因子内源性修复EC，正如我们随后的体外研究所证明的那样。基于这些研究结果，hBM-EPCs可以分泌细胞外囊泡，其可以包含并转移不同的囊泡生物分子以维持EC功能。该研究旨在表征源自hBM-EPCs的细胞外囊泡（EV）作为ALS中内皮修复的潜在无细胞疗法。在不同培养时间从hBM-EPC培养基中分离EV，并评价囊泡性质。研究了EV对ALS小鼠血浆暴露的小鼠脑内皮细胞（mBEC）的保护作用。在体外测定来自GFP转染的hBM-EPCs的EV在EC中的摄取和阻断。结果表明，从hBM-EPCs中分离的EV作为纳米囊泡显著降低了来自病理环境的mBEC损伤，并且这些EV被细胞摄取。阻断EV上的β1整联蛋白可防止mBEC中囊泡的内化。总之，这些结果为hBM-EPC衍生的EV作为ALS中内皮修复的新型无细胞治疗剂的潜力提供了证据。虽然确定hBM-EPC衍生的EV的翻译潜力将需要在体内进行评估，但该体外研究代表了向基于细胞外囊泡的方法修复ALS中受损微血管内皮的一步。
Repairing the damaged blood-CNS-barrier in amyotrophic lateral sclerosis (ALS) is necessary to prevent entry of detrimental blood-borne factors contributing to motor neuron dysfunction. Recently, we showed benefits of human bone marrow endothelial progenitor cell (hBM-EPC) transplantation into symptomatic ALS mice on barrier restoration by replacing damaged endothelial cells (ECs). Additionally, transplanted cells may endogenously repair ECs by secreting angiogenic factors as our subsequent in vitro study demonstrated. Based on these study results, hBM-EPCs may secrete extracellular vesicles, which may contain and transfer diverse vesicular biomolecules towards maintenance of EC functionality. The study aimed to characterize extracellular vesicles (EVs) derived from hBM-EPCs as potential cell-free therapeutics for endothelium repair in ALS. EVs were isolated from hBM-EPC media at different culture times and vesicle properties were evaluated. The protective effects of EVs on mouse brain endothelial cell (mBEC) exposed to ALS mouse plasma were investigated. Uptake and blockage of EVs from GFP-transfected hBM-EPCs in ECs were determined in vitro. Results showed that EVs isolated from hBM-EPCs as nanosized vesicles significantly reduced mBEC damage from the pathological environment and these EVs were taken up by cells. Blockage of β1 integrin on EVs prevented internalization of vesicles in mBECs. Together, these results provide evidence for potential of hBM-EPC-derived EVs as novel cell-free therapeutics for repair of endothelium in ALS. Although determining translational potential of hBM-EPC-derived EVs will require evaluation in vivo, this in vitro study represents a step towards an extracellular vesicle-based approach for repair of the damaged microvascular endothelium in ALS.
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影响因子：
5.3
作者：
Ehrhart J;Sanberg PR;Garbuzova-Davis S
通讯作者：
Garbuzova-Davis S
影响因子：
5.3
作者：
Garbuzova-Davis S;Haller E;Navarro S;Besong TE;Boccio KJ;Hailu S;Khatib M;Sanberg PR;Appel SH;Borlongan CV
通讯作者：
Borlongan CV
影响因子：
3.3
作者：
Cantaluppi, Vincenzo;Biancone, Luigi;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
4.6
作者：
Garbuzova-Davis S;Kurien C;Thomson A;Falco D;Ahmad S;Staffetti J;Steiner G;Abraham S;James G;Mahendrasah A;Sanberg PR;Borlongan CV
通讯作者：
Borlongan CV