Abstract
Mesenchymal stem cells (MSCs) have been shown to play therapeutic effect in traumatic brain injury (TBI). To augment the therapeutic effect, MSCs could be engineered to over-express genes that are beneficial for treatment. In the present study, we over-expressed hypoxia inducible factor (HIF)-1alpha in bone marrow derived MSCs (BM-MSCs) and sought to investigate whether HIF-1alpha could enhance the therapeutic effect of MSCs in a mouse model of TBI. Balb/c mice were subjected to controlled cortical impact injury and MSCs were transplanted intravenously at 6 h after injury. The lesion volume and brain water content were measured and the neurological function was assessed by modified neurologic severity score tests. Double-labeled immunofluorescence for BrdU and NeuU was performed to determine angiogenesis and neurogenesis. The expression of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) was measured by quantitative RT-PCR and western blotting. After TBI, mice received BM-MSCs over-expressing HIF-1alpha showed significantly more functional recovery, reduced brain damage, increased angiogenesis and neurogenesis and increased expression of VEGF and EPO, compared with control mice or mice treated with non-transduced BM-MSCs. Over-expression of HIF-1alpha enhanced BM-MSCs induced improvement of neurological recovery after TBI, by stimulating angiogenesis and neurogenesis.