Abstract 701: Mesenchymal Stem Cells Overexpressing FGF21 Improve Functional Recovery After Traumatic Brain Injury

Abstract

Traumatic Brain Injury (TBI) is a progressive and complex brain injury that results in many adverse and long term neurological consequences. Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator that has emerged as a therapeutic agent for the treatment of neurodegenerative diseases and brain injuries, as it has been shown to exhibit neuroprotective effects, promote remyelination, enhances angiogenesis, and to stimulate the neurite growth of glia-like cells. In this study, MSCs were genetically engineered to overexpress fibroblast growth factor 21 (FGF21) in order to improve their efficacy in TBI. MSCs overexpressing FGF21 (MSC-FGF21) were transplanted to mouse brain by intracerebroventricular (ICV) injection 24 hours after TBI. Spatial learning and memory tests were performed to examine the effects of MSC-FGF21 at 24 hours following controlled cortical impact (CCI) insult in TBI mice model. We found the FGF21 levels were reduced in the hippocampus of vehicle- treated group mice and that MSC-FGF21 treatment restored the FGF21 level significantly. MSC-FGF21 treatment significantly reduced spatial learning/memory decline at 21 days post injury as measured in the Morris water maze test. Both MSC-mCherry (vehicle control) and MSC-FGF21 treatments induced a significant improvement in short term memory formation as determined by the novel object recognition test (NOR) after 14 days of injury. In addition, MSC-FGF21treatment significantly increased the impaired neurogenesis and restored the dendritic process and morphology of immature neurons in the hippocampal dentate gyrus (DG). Taken together, these data provide compelling evidence that MSC-FGF21 treatment promotes neurogenesis and hippocampal neuroplasticity following TBI insult.