Influence of glioma cells on a new co-culture in vitro blood–brain barrier model for characterization and validation of permeability

The blood–brain barrier plays an important role in protecting the brain from injury and diseases, but also restrains the delivery of potential therapeutic drugs for the treatment of brain illnesses, such as tumors. Glioma is most common cancer type of central nervous system in adults and the most lethal in children. The treatment is normally poor and ineffective. To better understand the ability of drug delivery systems to permeate this barrier, a blood–brain barrier model using human brain endothelial cells and a glioma cell line is herein proposed. The consistent trans-endothelial electrical values, immunofluorescence and scanning electronic microscopy showed a confluent endothelial cell monolayer with high restrictiveness. Upon inclusion of glioma cell line, the trans-endothelial electrical resistance decreased, with consequent increase of apparent permeability of fluorescein isothiocyanate dextran used as model drug, revealing a reduction of the barrier robustness. In addition, it was demonstrated a cell shape modification in the co-culture, with loss of tight junctions. The microenvironment of co-cultured model presented significant increase of of CCL2/MCP-1 and IL-6 production, correlating with the modulation of permeation. The results encourage the use of the proposed in vitro model as a screening tool when performing drugs permeability for the treatment of disorders among the central nervous system.

Development of in vitro pathological model using immortalized human brain capillary endothelial cell line (hCMEC/D3) co-culture with glioma cell line (U87 cell line). After one week, different qualitative and quantitative methodologies were performed. The results indicated that glioma cell line had an impact on the endothelial barrier.Figure optionsDownload high-quality image (182 K)Download as PowerPoint slide