Abstract
The placental barrier is a multilayered cellular structure that serves as a permeable barrier between fetal and maternal blood circulation. Establishment of an in vitro system for the analysis of placental barrier function is of great interest in the pharmacokinetic study, because the barrier regulates the permeability not only of nutrients and metabolites but also of drugs and chemicals harmful to the developing fetus. A number of studies have been performed using a confluent monolayer of human placental barrier cells cultured on porous membrane support and, in most of the studies, the placental material transport assay is carried out under the static culture condition, although the barrier cells are continuously exposed to the maternal blood flow in vivo. These conventional assay systems are too simple to recapitulate the in vivo barrier property due to the lack of some tissue environmental factors such as structural arrangement of cells, cell-cell interactions, and mechanical stimuli in the tissue. Moreover, species differences of the placental structure make the animal experiments difficult to extrapolate the findings to human. From these reasons, permeability assay system with highly functional placental barrier has been expected to be developed. In this review, we introduce the bio-fabrication of human placental barrier structure integrated with microfluidic system which we reported recently. Microvillous surface of the placental barrier is successfully induced by utilizing fluid shear stress, which resulted in the restricted localization of glucose transporters to the induced microvilli. This polarized localization pattern of glucose transporters can’t be achieved under the conventional static culture system. We further describe the recent progress of placental barrier chip and the prospects for the use of microfluidic system as an analytical system of placental drug transport.
