Transfection of primary brain capillary endothelial cells for protein synthesis and secretion of recombinant erythropoietin: a strategy to enable protein delivery to the brain

摘要: Treatment of chronic disorders affecting the central nervous system (CNS) is complicated by inability drugs to cross blood-brain barrier (BBB). Non-viral gene therapy applied brain capillary endothelial cells (BCECs) denotes a novel approach overcome restraints in this passage, as turning BCECs into recombinant protein factories transfection could result secretion further brain. The present study aims investigate possibility transfecting primary rat (RBECs) for synthesis and neuroprotective erythropoietin (EPO). We previously showed that 4% RBECs with BBB properties can be transfected without disrupting integrity vitro, but it questioned whether sufficient enable at therapeutic levels. examined various vectors, regard increasing efficiency integrity. Lipofectamine 3000™ was most potent vector compared polyethylenimine (PEI) Turbofect. When co-cultured astrocytes, genetically modified secreted EPO cell culture medium both luminally abluminally, despite lower levels reaching abluminal chamber, amount evolve biological effect on astrocytes cultured side terms upregulated expression brain-derived neurotropic factor (BDNF). In conclusion, non-viral leads signifies method proteins target inside CNS otherwise omitted due BBB.