Biology subjects

Moerkens, R.

Publications and source records attributed to Moerkens, R..

3 recordsLinked to original sources

bioRxiv2026

Comparison of hiPSC-derived hepatic organoids and liver-on-a-chip systems reveal microenvironment-driven maturation

Human liver organoids (HLOs) and liver-on-a-chip (LoC) systems are emerging as physiologically relevant human models for studying liver function, disease, and drug metabolism, often in combination with human induced pluripotent stem cell (hiPSC)-derived tissues. However, hiPSC-derived models often display batch-to-batch variation and incomplete maturation, and the contribution of microfluidic flow to hepatic maturation remains insufficiently characterized. Here, we developed a cryopreservable and scalable workflow to generate hiPSC-derived hepatic organoids that can be directly matured to either static HLOs or LoC systems, enabling matched comparison of both platforms. Transcriptomic and functional characterization revealed progressive hepatic maturation during organoid differentiation, including increased expression of liver-specific metabolic pathways, enhanced albumin secretion, and increased CYP3A4 activity. Compared to mature HLOs, LoCs exposed to continuous microfluidic flow exhibited transcriptomic profiles suggesting further maturation, with increased enrichment of pathways related to lipid metabolism, xenobiotic metabolism, transport, and tissue organization. These findings demonstrate that microfluidic perfusion promotes hepatic metabolic specialization compared to static organoid culture while maintaining donor-specific characteristics. Together, this study establishes a robust hiPSC-derived LoC platform and highlights the potential of flow-based systems for improved modeling of human liver physiology, disease mechanisms, and drug responses.

cell biology↗

bioRxiv2024

Intestine-on-chip enhances nutrient and drug metabolism and maturation of iPSC-derived intestinal epithelial cells relative to organoids and Transwells

The human intestinal epithelial barrier is shaped by various biological and biomechanical influences such as growth factor gradients and the flow of intestinal contents. Exposure to these cues in vitro impacts the cell type composition and function of adult stem cell (ASC)-derived intestinal epithelial cells, but their effect on human induced pluripotent stem cell (hiPSC)-derived cells is largely unexplored. Here, we characterize and 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 in microfluidic intestine-on-chip systems. We demonstrate that inhibition and activation of the WNT, BMP, NOTCH and MAPK pathways regulates the presence of dividing, absorptive and secretory epithelial lineages within these systems, as has been described for ASC-based systems. Upon differentiation, intestinal epithelial organoids and monolayers in Transwell systems expressed genes involved in important intestinal functions, including digestive enzymes, nutrient transporters and members of the Cytochrome P450 family implicated in drug metabolism. However, the dynamic microenvironment of the intestine-on-chip system induced the strongest upregulation of these genes, with an expression profile that suggests a more mature developmental state. Overall, these results underscore the value of hiPSC-derived intestinal epithelial cells for modeling important functions of the human intestinal epithelial barrier and facilitates the selection of relevant culture conditions for specific applications.

cell biology↗

bioRxiv2024

An iPSC-derived small intestine-on-chip with self-organizing epithelial, mesenchymal and neural cells

Human induced pluripotent stem cell (hiPSC)-derived intestinal organoids are valuable tools for researching developmental biology and personalized therapies, but their closed topology and relative immature state limits their applications. Here we use organ-on-chip technology to develop a hiPSC-derived intestinal barrier with apical and basolateral access in a more physiological in vitro microenvironment. To replicate growth factor gradients along the crypt- villus axis, we locally exposed the cells to expansion and differentiation media. In these conditions, intestinal epithelial cells self-organize into villus-like folds with physiological barrier integrity and myofibroblast and neural subtypes emerge and form a layer in the bottom channel underneath the epithelial tissue. The growth factor gradients efficiently balance dividing and mature cell types and induce an intestinal epithelial composition, including absorptive and secretory lineages, resembling the composition of the human adult small intestine. The result is a well-characterized hiPSC-derived intestine-on-chip system that can facilitate personalized studies on physiological processes and therapy development in the human small intestine.

cell biology↗