Iris Kulbatski in The Scientist: The gut’s sensory system is a touchy subject thanks to specialized epithelial cells that line the gut and behave like touch sensors in the skin.1 These cells are sensitive to mechanical stimuli and communicate information about “gut feelings” to neurons in the gut as well as those that send messages to the brain.2 To understand the neuro-epithelial connections that conduct the grand symphony of digestion, a team of scientists at the Mayo Clinic orchestrated a unique collaboration of their own, combining their expertise in microfluidics, organs-on-a-chip, epithelial organoids, enteric nerves, and gut sensing.
In a study published in Microsystems & Nanoengineering, the researchers described a new microfluidic coculture platform that mimics the anatomy of gut tissue by modeling neuro-epithelial connectivity.3 This device allows scientists to study the subtle ways in which neurons and epithelial cells interact, which until now has been challenging because of the variable cell culture conditions needed to grow these different cell types.
“In many ways, it recapitulates the [gastrointestinal] system because the cell bodies of neurons within the gut wall are in a different layer, surrounded by a capsule that maintains the microenvironment and allows those axons to grow towards the epithelial cells,” said David Linden, a Mayo Clinic physiologist and biomedical engineer, and coauthor of this study.
The device, constructed by Alexander Revzin, a biomedical engineer at Mayo Clinic, has two separate chambers, one of which holds gut epithelial organoids and the other intestinal neurons. These reservoirs are separated by microgrooves that act as a thoroughfare for thin neuronal projections, supporting interactions between gut epithelial cells and neurons, while keeping the cell bodies and local microenvironments separate.
Using time-lapse microscopy, the researchers found that the cultured colon organoids formed an epithelial layer and that the intestinal neurons sent projections across the microgrooves into the adjacent chamber, where they connected with the epithelial cells. The mere presence of epithelial cells was enough to act as a cellular conductor’s wand to synchronize the biomolecular melody and boost the density of these projections on the epithelial side of the device. “Epithelia are very conscious of their own environment and space,” said Arthur Beyder, a Mayo Clinic gastroenterologist and biomedical engineer, and coauthor of this study. “If we didn’t have epithelia on one side, the neurons grew very differently. We’d like to understand the conversation that happens between these two systems.”
More here.
