Gut motility disorders such as gastroparesis and irritable bowel syndrome occur frequently and are associated with considerable morbidity. These disorders are poorly understood from a pathophysiology standpoint due to a lack of effective in vitro human gut models. Similarly, interstitial cells of Cajal (ICC), the pacemaker cells of the gut, are integral to gut motility yet there is no clear consensus as to their precise role in motility disorders. An in vitro model of normal human ICC function will therefore be invaluable to enhance our understanding of normal gut motility while also providing a tool for understanding how perturbations in ICC biology impact on motility disorders.
In an attempt to establish an in vitro human model of ICC and gut motility, human pluripotent stem cells were differentiated to intestinal organoids via exposure to successive growth factors involved in gut development. Concurrent bioinformatics analysis of ICC gene expression datasets identified a number of cell surface proteins, ion channels, and transcription factors not previously implicated in ICC function. The expression of these genes, together with recognized ICC marker genes, within the intestinal organoids is being analysed via PCR and immunofluorescence. Data from these studies will help determine whether the intestinal organoid differentiation conditions are a suitable model for investigation of ICC and their role in normal and diseased gut motility.