Work

Gene expression profiling reveals enhanced nutrient and drug metabolism and maturation of hiPSC-derived intestine-on-chip relative to organoids and Transwells

Year: 2025

Type: article

Abstract: The human intestinal epithelial barrier is shaped by biological and biomechanical cues, including growth factor gradients and fluid flow. While these factors are known to affect adult stem cell (ASC)-derived intestinal epithelial cells in vitro, their impact on human induced pluripotent stem cell (hiPSC)-derived cells is largely unexplored. Here, we compare the cellular composition and gene expression profiles of hiPSC-derived intestinal epithelial cells exposed to various medium compositions and cultured as organoids, in Transwell and microfluidic intestine-on-chip systems. Modulating key signaling pathways (WNT, NOTCH, bone morphogenetic protein [BMP], and mitogen-activated protein kinase [MAPK]) influenced the presence of dividing, absorptive, and secretory epithelial lineages. Upon differentiation, intestinal epithelial cells expressed genes encoding digestive enzymes, nutrient transporters, and drug-metabolizing enzymes. Notably, these pathways were most enhanced in the intestine-on-chip system, along with an expression profile that suggests a more mature state. These findings highlight the potential of hiPSC-derived intestinal cells to model important intestinal functions and guide the selection of optimal culture conditions for specific applications.

Source: Stem Cell Reports

DOI: 10.1016/j.stemcr.2025.102715