Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease

The enteric nervous system (ENS) is essential to normal gut function and works to some extent independently from other neuronal circuits. Lorenz Studer and colleagues have developed a differentiation protocol for human pluripotent stem cells to obtain ENS progenitors and a range of neurons found in the ENS. They show that these can migrate and graft to the gut of a chick embryo and adult mouse colon, including in a mouse model of Hirschsprung disease, in which they observe a functional rescue. The authors also show that ENS precursors derived from patients affected by Hirschsprung disease can be used to screen for drugs that can modulate the properties of these cells.