Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei 110, Taiwan.
Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 110, Taiwan.
Int J Mol Sci. 2019 May 28;20(11):2624. doi: 10.3390/ijms20112624.
Mesenchymal stem cells (MSCs) are emerging as a potential therapeutic intervention for brain injury due to their neuroprotective effects and safe profile. However, the homing ability of MSCs to injury sites still needs to be improved. Fibroblast Growth Factor 21 (FGF21) was recently reported to enhance cells migration in different cells type. In this study, we investigated whether MSCs that overexpressing FGF21 (MSC-FGF21) could exhibit enhanced homing efficacy in brain injury. We used novel Molday IONEverGreen™ (MIEG) as cell labeling probe that enables a non-invasive, high-sensitive and real-time MRI tracking. Using a mouse model of traumatic brain injury (TBI), MIEG labeled MSCs were transplanted into the contralateral lateral ventricle followed by real-time MRI tracking. FGF21 retained MSC abilities of proliferation and morphology. MSC-FGF21 showed significantly greater migration in transwell assay compared to control MSC. MIEG labeling showed no effects on MSCs' viability, proliferation and differentiation. Magnetic resonance imaging (MRI) revealed that FGF21 significantly enhances the homing of MSC toward injury site. Histological analysis further confirmed the MRI findings. Taken together, these results show that FGF21 overexpression and MIEG labeling of MSC enhances their homing abilities and enables non-invasive real time tracking of the transplanted cells, provides a promising approach for MSC based therapy and tracking in TBI.
间充质干细胞（MSCs）因其具有神经保护作用和安全特性，正成为治疗脑损伤的一种有潜力的治疗方法。然而，MSCs 向损伤部位的归巢能力仍需要提高。成纤维细胞生长因子 21（FGF21）最近被报道可增强不同细胞类型的细胞迁移能力。在本研究中，我们研究了过表达 FGF21 的 MSCs（MSC-FGF21）是否能够增强脑损伤后的归巢效率。我们使用新型 Molday IONEverGreen™（MIEG）作为细胞标记探针，能够进行非侵入性、高灵敏度和实时 MRI 跟踪。使用创伤性脑损伤（TBI）的小鼠模型，将 MIEG 标记的 MSCs 移植到对侧侧脑室，然后进行实时 MRI 跟踪。FGF21 保留了 MSC 的增殖和形态学能力。与对照 MSC 相比，MSC-FGF21 在 Transwell 测定中显示出显著更大的迁移能力。MIEG 标记对 MSC 的活力、增殖和分化没有影响。磁共振成像（MRI）显示，FGF21 显著增强了 MSC 向损伤部位的归巢。组织学分析进一步证实了 MRI 的发现。总之，这些结果表明，FGF21 的过表达和 MSC 的 MIEG 标记增强了它们的归巢能力，并能够对移植细胞进行非侵入性实时跟踪，为 TBI 中的 MSC 治疗和跟踪提供了一种有前途的方法。
