Yan Sen, Hu Ke, Zhang Miao, Sheng Jingyi, Xu Xueqin, Tang Shijia, Li Yan, Yang Sheng, Si Guangxiang, Mao Yu, Zhang Yi, Zhang Feimin, Gu Ning
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, Jiangsu, China.
Laboratory of Oral Regenerative Medicine Technology, School of Biomedical Engineering and Informatics, Department of Biomedical Engineering, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
Bioact Mater. 2022 May 1;19:418-428. doi: 10.1016/j.bioactmat.2022.04.024. eCollection 2023 Jan.
Labeling of mesenchymal stem cells (MSCs) with superparamagnetic iron oxide nanoparticles (SPIONs) has emerged as a potential method for magnetic resonance imaging (MRI) tracking of transplanted cells in tissue repair studies and clinical trials. Labeling of MSCs using clinically approved SPIONs (ferumoxytol) requires the use of transfection reagents or magnetic field, which largely limits their clinical application. To overcome this obstacle, we established a novel and highly effective method for magnetic labeling of MSC spheroids using ferumoxytol. Unlike conventional methods, ferumoxytol labeling was done in the formation of a mechanically tunable biomimetic hydrogel-induced MSC spheroids. Moreover, the labeled MSC spheroids exhibited strong MRI T2 signals and good biosafety. Strikingly, the encapsulated ferumoxytol was localized in the extracellular matrix (ECM) of the spheroids instead of the cytoplasm, minimizing the cytotoxicity of ferumoxytol and maintaining the viability and stemness properties of biomimetic hydrogel-induced MSC spheroids. This demonstrates the potential of this method for post-transplantation MRI tracking in the clinic.
用超顺磁性氧化铁纳米颗粒（SPIONs）标记间充质干细胞（MSCs）已成为组织修复研究和临床试验中对移植细胞进行磁共振成像（MRI）追踪的一种潜在方法。使用临床批准的SPIONs（ ferumoxytol）标记MSCs需要使用转染试剂或磁场，这在很大程度上限制了它们的临床应用。为了克服这一障碍，我们建立了一种使用ferumoxytol对MSC球体进行磁性标记的新颖且高效的方法。与传统方法不同，ferumoxytol标记是在机械可调的仿生水凝胶诱导的MSC球体形成过程中完成的。此外，标记后的MSC球体表现出强烈的MRI T2信号和良好的生物安全性。令人惊讶的是，包封的ferumoxytol定位于球体的细胞外基质（ECM）而非细胞质中，从而将ferumoxytol的细胞毒性降至最低，并维持了仿生水凝胶诱导的MSC球体的活力和干性。这证明了该方法在临床上用于移植后MRI追踪的潜力。
