Molecular Imaging Lab, Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Interventional Radiology Institute, Sun Yat-sen University, Guangzhou 510630, China.
PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Biomaterials. 2014 Sep;35(28):8249-60. doi: 10.1016/j.biomaterials.2014.06.014. Epub 2014 Jun 26.
MSC's transplantation is a promising cell-based therapy for injuries in regenerative medicine, and in vivo visualization of transplanted MSCs with noninvasive technique is essential for the tracking of cell infusion and homing. A new cationic polymer, poly(ethylene glycol)-block-poly(l-aspartic acid)-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (PAI/SPION), was constructed as a magnetic resonance imaging (MRI)-visible non-viral vector for the delivery of plasmids DNA (pDNA) encoding for luciferase and red fluorescence protein (RFP) as reporter genes into MSCs. As a result, the MSCs were labeled with SPION and reporter genes. The PAI/SPION complexes exhibited high transfection efficiency in transferring pDNA into MSCs, which resulted in efficient luciferase and RFP co-expression. Furthermore, the complexes did not significantly affect the viability and multilineage differentiation capacity of MSCs. After the labeled MSCs were transplanted into the rats with acute liver injury via the superior mesenteric vein (SMV) injection, the migration behavior and organ-specific accumulation of the cells could be effectively monitored using the in vivo imaging system (IVIS) and MRI, respectively. The immunohistochemical analysis further confirmed that the transplanted MSCs were predominantly distributed in the liver parenchyma. Our results indicate that the PAI/SPION is a MRI-visible gene delivery agent which can effectively label MSCs to provide the basis for bimodal bioluminescence and MRI tracking in vivo.
MSC 的移植是再生医学中一种很有前途的基于细胞的治疗方法,用非侵入性技术对移植的 MSC 进行体内可视化对于跟踪细胞输注和归巢至关重要。一种新的阳离子聚合物,聚(乙二醇)-嵌段-聚(L-天冬氨酸)-接枝聚亚乙基亚胺功能化超顺磁性氧化铁纳米粒子(PAI/SPION),被构建为一种磁共振成像(MRI)可见的非病毒载体,用于递送编码荧光素酶和红色荧光蛋白(RFP)的质粒 DNA(pDNA)作为报告基因进入 MSC。结果,MSC 被 SPION 和报告基因标记。PAI/SPION 复合物在将 pDNA 转染到 MSC 中表现出高转染效率,导致荧光素酶和 RFP 的有效共表达。此外,复合物对 MSC 的活力和多谱系分化能力没有显著影响。将标记的 MSC 通过肠系膜上静脉(SMV)注射移植到急性肝损伤大鼠体内后,分别使用体内成像系统(IVIS)和 MRI 可以有效地监测细胞的迁移行为和器官特异性积累。免疫组织化学分析进一步证实,移植的 MSC 主要分布在肝实质中。我们的结果表明,PAI/SPION 是一种 MRI 可见的基因传递剂,可有效标记 MSC,为体内双模态生物发光和 MRI 跟踪提供基础。