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A novel polymeric micelle used for in vivo MR imaging tracking of neural stem cells in acute ischemic stroke

机译：用于急性缺血性卒中神经干细胞体内 MR成像追踪的新型聚合物胶束

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Transplantation of neural stem cells (NSCs) is a promising treatment strategy for acute ischemic stroke. In vivo tracking of the therapeutic stem cells in the host brain after transplantation is essential not only to ensure the safety and efficacy of the treatment, but also to better understand their migrational dynamics and regeneration potential. Many polymeric nanoparticles have been developed to label stem cells for in vivo tracking by magnetic resonance imaging (MRI), optical imaging (OI) or other imaging modalities. However, the non-degradability and presence of cellular toxicity of the nanoparticles restrict their clinical applications. In this study, we developed a novel cationic polymeric micelles based on amphipathic polymer of biodegradable hydrophilic poly(aspartic acid-dimethylethanediamine) (PAsp(DMA)) that were conjugated with two molecules of hydrophobic cholic acid (CA) by lysine. Image labels, superparamagnetic iron oxide nanoparticles (SPIONs) and fluorescent nile red were simultaneously loaded into the micelles to label NSCs. The labeling capacity, efficiency and cytotoxicity of the cationic micelles were determined. The in vivo MRI tracking of the therapeutic NSCs in acute ischemic stroke was also explored. Our results showed that this type of cationic polymeric micelles achieved a high efficient and safe labeling of NSCs and resulted in reliable in vivo MRI tracking of therapeutic stem cells in acute ischemic stroke, but without detrimental effect. The cationic, biodegradable polymeric micelles are highly translatable for clinical application and can be used as a versatile nanoplatform for stem cell labeling and subsequently in vivo tracking in regenerative medicine.
机译：神经干细胞（NSC）的移植是急性缺血性卒中的一种有前途的治疗策略。体内体内追踪移植后宿主脑中的治疗性干细胞不仅对于确保治疗的安全性和有效性至关重要，而且对于更好地了解其迁移动力学和再生潜力至关重要。已经开发出许多聚合物纳米颗粒来标记干细胞，以通过磁共振成像（MRI），光学成像（OI）或其他成像方式进行体内跟踪。然而，纳米颗粒的不可降解性和细胞毒性的存在限制了它们的临床应用。在这项研究中，我们开发了一种基于可生物降解的亲水性聚天冬氨酸-二甲基乙二胺（PAsp（DMA））的两亲性聚合物的新型阳离子聚合物胶束，该聚合物与赖氨酸的两个疏水性胆酸（CA）分子共轭。将图像标签，超顺磁性氧化铁纳米颗粒（SPIONs）和荧光尼罗红同时装入胶束中，以标记NSC。测定了阳离子胶束的标记能力，效率和细胞毒性。还探讨了急性缺血性中风中治疗性NSC的体内 MRI追踪。我们的结果表明，这种类型的阳离子聚合物胶束对NSC进行了高效，安全的标记，并在急性缺血性中风中对治疗性干细胞进行了可靠的体内 MRI追踪，但没有有害作用。阳离子，可生物降解的聚合物胶束在临床应用中具有很高的可翻译性，可以用作干细胞标记和随后在再生医学中的体内追踪的通用纳米平台。

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