Stem Cell Therapy for Enteric Neuropathies

Enteric neuropathies, such as Hirschsprung disease (HSCR), comprise a number of severe diseases of the enteric nervous system (ENS) of the gastrointestinal (GI) tract with, as yet, no cures. The replacement of absent or diseased enteric neurons via stem cell transplantation directly into diseased gut represents a novel, curative therapy. This idea is supported by over two decades of preclinical research, carried out mainly in mice, demonstrating that neural crest-derived stem cells can be isolated from the gut, expanded in culture, and transplanted into gut in vivo where they migrate, proliferate, differentiate, and become functionally active. Here, we review some of the learnings from these studies, outlining the diseases potentially amenable to stem cell replacement therapy, the animals used to model disease, the different types of stem cells that could be used for therapy, the methodologies developed to prepare and deliver stem cells to the gut, and cell safety considerations. With the significant progress that has already been made by the field, the aim of developing a curative stem cell therapy for devastating diseases of the enteric nervous system is rapidly approaching reality.