Human in vitro blood barrier models: architectures and applications

Abstract

Blood barriers serve as key points of transport for essential molecules as well as lines of defense to protect against toxins. In vitro modeling of these barriers is common practice in the study of their physiology and related diseases. This review describes a common method of using an adaptable, low cost, semipermeable, suspended membrane to experimentally model three blood barriers in the human body: the blood-brain barrier (BBB), the gut-blood barrier (GBB), and the air-blood barrier (ABB). The GBB and ABB both protect from the outside environment, while the BBB protects the central nervous system from potential neurotoxic agents in the blood. These barriers share several commonalities, including the formation of tight junctions, polarized cellular monolayers, and circulatory system contact. Cell architectures used to mimic barrier anatomy as well as applications to study function, dysfunction, and response provide an overview of the versatility enabled by these cultural systems.

Keywords: air-blood barrier; blood barrier; blood-brain barrier; gut-blood barrier; transwell.

Figure 1.

Cell placement within barrier models employing a semipermeable, suspended membrane. a) single cell cultured in the apical chamber, b) contact coculture, c) non-contact coculture, and d) multicellular contact and non-contact coculture. Created with BioRender.com.

Figure 2.

Physiological locations of cell types in the BBB. Endothelial cells (red) are bordered by pericytes (orange) and surrounded by astrocyte (green) end-feet, which are influenced by neurons (blue) to regulate cerebral blood flow. Created with BioRender.com..

Figure 3.

Physiological locations of cell types in the GBB. a layer containing epithelial cells (yellow) is exposed to the gut and is in contact with endothelial cells (red). A variety of immune cells (purple) reside in the blood and can extravasate into the gut. Created with BioRender.com.

Figure 4.

Physiological locations of cell types in the ABB. Epithelial cells (yellow) have direct contact with outside air, while fibroblasts (brown) are positioned between the epithelial cells and endothelial cells (red). Immune cells (purple) are found in the interstium, circulation, and capillary lumen. Created with BioRender.com.