Abstract: Provided are new strategies, methods and systems, described herein as vasoactive intestinal peptide (VIP)-assisted air-liquid-interface (ALI) culture, to significantly increase the number of enteroendocrine (EEC) and enterochromaffin (EC) cells over the traditional submerged culture, while at the same time maintaining a high barrier integrity of monolayers. The new strategies, methods and systems overcome the limitations of the existing EEC enrichment methods by maintaining high cell viability and barrier integrity and without requiring complicated procedures of cocultures or genetic engineering/induction. The created EEC-enriched, contiguous monolayer platform acts as a robust analytical tool to enable functional studies of hormone secretion from EEC cells with high signal background ratio and repeatability.