Magnetically enhanced cell delivery for accelerating recovery of the endothelium in injured arteries.
Magnetically enhanced cell delivery for accelerating recovery of the endothelium in injured arteries.
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DOI：
10.1016/j.jconrel.2015.12.025
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发表时间：
2016-01-28
期刊：
影响因子：
--
通讯作者：
Chorny M
中科院分区：
文献类型：
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作者：
Adamo RF;Fishbein I;Zhang K;Wen J;Levy RJ;Alferiev IS;Chorny M
动脉损伤和内皮层破坏是用于治疗阻塞性血管疾病的介入手术的不可避免的后果。损伤后缓慢且通常不完全的内皮再生是严重的短期和长期并发症的主要原因，包括血栓形成、再狭窄和新动脉粥样硬化。快速内皮恢复有可能预防这些后遗症，为开发旨在加速再内皮化过程的策略提供了理论基础。目前的研究集中在磁性引导递送的内皮细胞（EC）功能与可生物降解的磁性纳米粒子（MNP）作为一种实验方法，实现快速和稳定的细胞归巢和扩张的支架动脉。EC负载聚乳酸为基础的MNP表现出很强的磁响应性，冷冻保存和快速扩张的能力，并有能力在增殖和接触抑制状态下分解内化的MNP。基于发射光谱中组装状态依赖性变化非侵入性监测的BODIPY 558/568标记的MNP的细胞内分解证明了细胞增殖速率依赖性动力学（平均分解速率：分裂和接触抑制EC中分别为每天6.6 ± 0.8%和3.6 ± 0.4%）。与磁引导使用一个短暂的暴露在一个统一的1千奥斯特场，稳定的本地化和随后的传播MNP功能化EC，显着增强相比，非磁性的交付条件，在支架大鼠颈动脉中观察。总之，磁引导输送是一种有前途的实验策略，用于加速血管成形术后支架血管的内皮细胞再生。
Arterial injury and disruption of the endothelial layer are an inevitable consequence of interventional procedures used for treating obstructive vascular disease. The slow and often incomplete endothelium regrowth after injury is the primary cause of serious short- and long-term complications, including thrombosis, restenosis and neoatherosclerosis. Rapid endothelium restoration has the potential to prevent these sequelae, providing a rationale for developing strategies aimed at accelerating the reendothelialization process. The present studies focused on magnetically guided delivery of endothelial cells (EC) functionalized with biodegradable magnetic nanoparticles (MNP) as an experimental approach for achieving rapid and stable cell homing and expansion in stented arteries. EC laden with polylactide-based MNP exhibited strong magnetic responsiveness, capacity for cryopreservation and rapid expansion, and the ability to disintegrate internalized MNP in both proliferating and contact-inhibited states. Intracellular decomposition of BODIPY558/568-labeled MNP monitored non-invasively based on assembly state-dependent changes in the emission spectrum demonstrated cell proliferation rate-dependent kinetics (average disassembly rates: 6.6 ± 0.8% and 3.6 ± 0.4% per day in dividing and contact-inhibited EC, respectively). With magnetic guidance using a transient exposure to a uniform 1-kOe field, stable localization and subsequent propagation of MNP-functionalized EC, markedly enhanced in comparison to non-magnetic delivery conditions, were observed in stented rat carotid arteries. In conclusion, magnetically guided delivery is a promising experimental strategy for accelerating endothelial cell repopulation of stented blood vessels after angioplasty.