Abstract

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.

Highlights

  • Traumatic brain injury (TBI) is the most common form of head injury and is estimated to result in death or hospital admission for more than 10 million people worldwide annually [1,2]

  • DisCcluinssicioanl interest has been focused on Mesenchymal stem cells (MSCs) therapy as a potential therapeutic approach for TBI, wherCelitnhiecatrleianttmereensttshaavsabielaebnlefoacruesleimd iotnedM

  • Our results demonstrated that overexpression of Fibroblast Growth Factor 21 (FGF21) significantly (p < 0.05) enhanced migration MSC in vitro in the Transwell assay (Figure 1E,F)

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Summary

Introduction

Traumatic brain injury (TBI) is the most common form of head injury and is estimated to result in death or hospital admission for more than 10 million people worldwide annually [1,2]. Deficits in learning and memory have been reported in several cognitive domains, including executive function, attention, working memory, episodic memory, verbal learning, and processing speed [4,5]. In both animal models and human studies, cognitive impairment following TBI has been correlated with neural atrophy and progressive cell death in the hippocampus and frontal cortex. A clinical trial has demonstrated that transplantation of bone marrow mononuclear cells in adults with severe TBI insult is a safe and feasible option for cell-based therapy in humans [10]

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