Barrier Functionality of Porcine and Bovine Brain Capillary Endothelial Cells

Abstract

Introduction: To date, isolated cell based blood-brain barrier (BBB) models have been widely used for brain drug delivery and targeting, due to their relatively proper bioelectrical and permeability properties. However, primary cultures of brain capillary endothelial cells (BCECs) isolated from different species vary in terms of bioelectrical and permeability properties. Methods: To pursue this, in the current investigation, primary porcine and bovine BCECs (PBCECs and BBCECs, respectively) were isolated and used as an in vitro BBB model. The bioelectrical and permeability properties were assessed in BCECs co-cultured with C6 cells with/without hydrocortisone (550 nM). The bioelectrical properties were further validated by means of the permeability coefficients of transcellular and paracellular markers. Results: The primary PBCECs displayed significantly higher trans-endothelial electrical resistance (~900 W.cm²) than BBCECs (~700 W.cm²) - both co-cultured with C6 cells in presence of hydrocortisone. Permeability coefficients of propranolol/diazepam and mannitol/sucrose in PBCECs were ~21 and ~2 (×10^-6 cm.sec^-1), where these values for BBCECs were ~25 and ~5 (×10^-6 cm.sec^-1). Conclusion: Upon our bioelectrical and permeability findings, both models display discriminative barrier functionality but porcine BCECs seem to provide a better platform than bovine BCECs for drug screening and brain targeting.

Keywords: Blood-brain barrier, Bioelectrical properties, Cell culture model, Brain targeting, Cell and tissue engineering