A multidimensional platform to support intestinal epithelial and immune cell co-culture

Detailed research into intestinal immune exposure to luminal contents, including nutrients and microbial metabolites, could be well supported by accurate and reproducible models of the human intestinal milieu. Animal models provide insights but are not fully predictive of human biology, while human correlative studies are hampered by the complexity of feedback signals from established immune reactions. Therefore, characterization of human nutrient uptake and immediate effects on intestinal health will benefit from ex vivo models that provide controlled experimental conditions and include relevant human cells.

This work introduces a novel platform that integrates key human immune cell types with intestinal epithelial cells (IECs), which provide both the barrier and the permissive interface between intestinal contents and immune cells. Specifically, cells from the small intestinal ileum are incorporated because this is a crucial site of immune system exposure, where Peyer's patches of the epithelial lining provide a permeable interface for luminal content sampling by sentinel dendritic cells (DCs) and macrophages. To support relevant cell-cell contact and co-culture, we have built and evaluated a custom three-dimensional matrix similar to the lamina propria and designed to support DCs and T cells in direct contact with the IECs. The material is produced by electrospinning polycaprolactone into a bilayer material with two pore types: small pores to support epithelial organization into a tightly organized monolayer that provides appropriate barrier function and large pores that provide access and movement for the large, migratory DCs.

As a result of cell co-culture on the bilayer material, the two cell types interact directly with each other in a manner more similar to in vivo biology. This structure enables an in vitro model where nutrients, commensal microbes, pathogens and other antigens can be introduced to the epithelium, and the innate and adaptive immune response can be evaluated.

This platform has the potential to provide a consistent and reproducible context for studies of nutrient effects on human intestinal health and inflammation.