Enhanced neuroprotective efficacy of bone marrow mesenchymal stem cells co-overexpressing BDNF and VEGF in a rat model of cardiac arrest-induced global cerebral ischemia.

摘要: Cardiac arrest-induced global cerebral ischemia injury (CA-GCII) usually leads to a poor neurological outcome without an effective treatment. Bone marrow-derived mesenchymal stem cells (BMMSCs) may provide potential cell-based therapy against neurologic disorders through induction of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth (VEGF). To optimize the neuroprotective efficacy BMMSCs further, in this study we have derived BMMSCs, which co-overexpress both BDNF VEGF, tested them for treatment CA-GCII rat model. Lentiviruses that express exon IV or VEGF-A were created using bicistronic shuttle vectors pLVX-IRES-ZsGreen1 pLVX-IRES-tdTomato, respectively. co-transduced with engineered lentiviruses co-overexpression VEGF along corresponding fluorescent protein reporters injected via jugular vein rats just recovered from cardiac arrest. Animals then scored neurofunctional deficits examined brain pathology gene expression relevant engraftment seven days after treatments. We demonstrate anchorage lentiviral vector-transduced co-overexpressed hippocampus temporal cortex significantly ameliorated improved performance transplantation. These findings proof concept further validation patients clinical practice future.