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聚簇超顺磁性氧化铁纳米颗粒标记的间充质干细胞在氨基糖苷类药物诱导的耳毒性小鼠模型中的生物分布

Biodistribution of poly clustered superparamagnetic iron oxide nanoparticle labeled mesenchymal stem cells in aminoglycoside induced ototoxic mouse model.

作者信息

Ahn Ye Ji, Yun Wan Su, Choi Jin Sil, Kim Woo Cheol, Lee Su Hoon, Park Dong Jun, Park Jeong Eun, Key Jaehong, Seo Young Joon

机构信息

Research Institute of Hearing Enhancement, Yonsei University Wonju College of Medicine, Wonju, 26426 South Korea.

Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, Gangwon-do 26426 South Korea.

出版信息

Biomed Eng Lett. 2021 Jan 8;11(1):39-53. doi: 10.1007/s13534-020-00181-6. eCollection 2021 Feb.

Abstract

Recently, application of stem cell therapy in regenerative medicine has become an active field of study. Mesenchymal stem cells (MSCs) are known to have a strong ability for homing. MSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) exhibit enhanced homing due to magnetic attraction. We have designed a SPION that has a cluster core of iron oxide-based nanoparticles coated with PLGA-Cy5.5. We optimized the nanoparticles for internalization to enable the transport of PCS nanoparticles through endocytosis into MSCs. The migration of magnetized MSCs with SPION by static magnets was seen in vitro. The auditory hair cells do not regenerate once damaged, ototoxic mouse model was generated by administration of kanamycin and furosemide. SPION labeled MSC's were administered through different injection routes in the ototoxic animal model. As result, the intratympanic administration group with magnet had the highest number of cells in the brain followed by the liver, cochlea, and kidney as compared to those in the control groups. The synthesized PCS (poly clustered superparamagnetic iron oxide) nanoparticles, together with MSCs, by magnetic attraction, could synergistically enhance stem cell delivery. The poly clustered superparamagnetic iron oxide nanoparticle labeled in the mesenchymal stem cells have increased the efficacy of homing of the MSC's to the target area by synergetic effect of magnetic attraction and chemotaxis (SDF-1/CXCR4 axis). This technique allows delivery of the stem cells to the areas with limited vasculatures. The nanoparticle in the biomedicine allows drug delivery, thus, the combination of nanomedicince together with the regenerative medicine will provide highly effective therapy.

摘要

最近,干细胞疗法在再生医学中的应用已成为一个活跃的研究领域。已知间充质干细胞(MSCs)具有很强的归巢能力。用超顺磁性氧化铁纳米颗粒(SPIONs)标记的间充质干细胞由于磁吸引力而表现出增强的归巢能力。我们设计了一种SPION,其具有基于氧化铁的纳米颗粒簇核心,表面包覆有PLGA-Cy5.5。我们对纳米颗粒进行了内化优化,以使PCS纳米颗粒能够通过内吞作用转运到间充质干细胞中。在体外观察到了用静态磁铁引导的带有SPION的磁化间充质干细胞的迁移。听觉毛细胞一旦受损就不会再生,通过给予卡那霉素和速尿建立了耳毒性小鼠模型。在耳毒性动物模型中通过不同的注射途径给予SPION标记的间充质干细胞。结果,与对照组相比,有磁体的鼓室内给药组在脑中的细胞数量最多,其次是肝脏、耳蜗和肾脏。合成的PCS(多簇超顺磁性氧化铁)纳米颗粒与间充质干细胞一起,通过磁吸引力可以协同增强干细胞递送。间充质干细胞中标记的多簇超顺磁性氧化铁纳米颗粒通过磁吸引力和趋化作用(SDF-1/CXCR4轴)的协同效应提高了间充质干细胞向靶区域归巢的效率。这项技术能够将干细胞递送至血管有限的区域。生物医学中的纳米颗粒可实现药物递送,因此,纳米医学与再生医学的结合将提供高效的治疗方法。

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