Novel ‘Gut-on-a-Chip’ Model Uncovers Biomarker for Immunotherapy in Melanoma

A team of researchers from the European Institute of Oncology and the Politecnico di Milano developed the novel “gut-on-a-chip”: a miniature model of the human intestine on a chip-sized device capable of reproducing the main features of intestinal inflammation as a biomarker for response to immune checkpoint inhibitors in patients with melanoma.

The results were published in Nature Biomedical Engineering.

The research group developed a model that was suitable for real-time multiomic detections, which consists of a vascular channel seeded with human microvascular endothelial cells and an intestinal channel with intestinal organoids derived from human induced pluripotent stem cells separated by an extracellular matrix–like gel layer.

They adapted previous methods to seed their gut-on-a-chip with human induced pluripotent stem cell (hiPSC)–derived intestinal organoids, including fecal microbiome. They then investigated the impact of peristaltic-like movements in their novel hiPSC-derived gut-on-a-chip.

The team uncovered epithelium-specific biomarkers and microbial factors that correlate with clinical outcomes in patients with melanoma and found that the microbiome of nonresponders has a reduced ability to buffer cellular stress and self-renew.

The researchers noted that “findings show that the response of melanoma to immunotherapy can be predicted based on effects elicited by patient-derived faecal samples on our gut-on-a-chip, which is also suitable for dissecting mechanistic details underlying the interactions of different components of the microbiota with host and to foster their development into new therapeutics.”

Source

Nature Biomechanical Engineering