Biological activity comparative evaluation of the gene-Activated bone substitutes made of octacalcium phosphate and plasmid DNA carrying VEGF and SDF genes: Part 1 - in vitro
High need for effective bone substitutes and drawbacks of the materials approved for clinical use determine the increasing activity of biomedical research in this area. We have developed gene-Activated bone substitutes consisting of a scaffold based on octacalcium phosphate (OCP) and one of the two variants of plasmid DNA carrying either a gene for vascular endothelial growth factor (VEGF) or two genes encoding VEGF and stromal derived factor- 1α (SDF-1α). The aim of the study was to evaluate the cytotoxicity of the gene-Activated materials and their components, as well as biological activity in vitro. We found that both OCP and gene-Activated bone substitutes did not have any cytotoxicity, but reduced the proliferative activity of human bone marrow-derived multipotent mesenchymal stromal cells: material with doublegene construct decreased cell culture doubling rate of 24.3% more compared with the material carrying plasmid DNA encoding only VEGF. Both gene-Activated materials led to an increase in therapeutic genes mRNA levels, but the material with double-gene system enhanced VEGF protein production greater. Thus, the gene-Activated bone substitutes characterized by the absence of cytotoxic properties and possessed a specific activity increasing expression of the therapeutic genes. However, further studies are needed to detail the identified characteristics and assess the feasibility of the defined biological action in vivo
