In one embodiment, the present invention is a method of creating a fully-human blood-brain barrier (BBB) model, comprising the steps of (a) obtaining a mixture of neural cells and brain microvascular endothelial cells (BMECs), wherein the neural cells and BMECs that comprise the mixture were produced from the differentiation of human pluripotent stem cells (hPSCs); (b) purifying BMECs from the mixture of neural cells and BMECs of step (a); and (c) co-cuituring the purified BMECs with a ceil type selected from the group consisting of pericytes, astrocytes and differentiated neural progenitor ceils (NPCs), wherein a blood brain barrier model is created. In another embodiment the present invention is a method of creating a retinoic acid (RA)-enhanced or RA-like compound-enhanced mammalian blood-brain barrier (BBB) model, comprising the steps of: (a) obtaining a mixture of neural cells and brain microvascular endothelial ceils (BMECs) in the presence of RA or RA-like compound, wherein the mixture of neural ceils and BMECs was produced from the differentiation of human pluripotent stem ceils (hPSCs); (b) purifying BMECs from the mixture of neural cells and BMECs; and co- cuituring the purified BMECs with a cell type selected from the group consisting of astrocytes, pericytes and differentiated neural progenitor ceils (NPCs), wherein a BBB model is created.