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Enhanced Homing of Mesenchymal Stem Cells Overexpressing Fibroblast Growth Factor 21 to Injury Site in a Mouse Model of Traumatic Brain Injury.

Rami Ahmad Shahror | Ahmed Atef Ahmed Ali | Chung-Che Wu | Yung-Hsiao Chiang | Kai-Yun Chen
International journal of molecular sciences | 2019

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.

Pubmed ID: 31142002

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ITK-SNAP (tool)

RRID:SCR_002010

Open source interactive software application for three dimentional medical images, manual delineation of anatomical regions of interest, and performing automatic image segmentation. Used for delineating anatomical structures and regions in MRI, CT and other 3D biomedical imaging data.

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Intramural Research Program (tool)

RRID:SCR_012734

A research program of the NIA which focuses on neuroscience, aging biology, and translational gerontology. The central focus of the program's research is understanding age-related changes in physiology and the ability to adapt to environmental stress, and using that understanding to develop insight about the pathophysiology of age-related diseases. The IRP webpage provides access to other NIH resources such as the Biological Biochemical Image Database, the Bioinformatics Portal, and the Baltimore Longitudinal Study of Aging.

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