Updates and Challenges in ENS Cell Therapy for the Treatment of Neurointestinal Diseases

Abstract

Neurointestinal diseases represent a significant challenge in clinical management with current palliative approaches failing to overcome disease and treatment-related morbidity. The recent progress with cell therapy to restore missing or defective components of the gut neuromusculature offers new hope for potential cures. This review discusses the progress that has been made in the sourcing of putative stem cells and the studies into their biology and therapeutic potential. We also explore some of the practical challenges that must be overcome before cell-based therapies can be applied in the clinical setting. Although a number of obstacles remain, the rapid advances made in the enteric neural stem cell field suggest that such therapies are on the near horizon.

Keywords: cell therapy; cell transplantation; enteric neural crest-derived cells; neurointestinal diseases; regenerative medicine.

Figure 1

An example of a cell-based treatment strategy for Hirschsprung disease, a congenital neurointestinal disorder. Enteric neurospheres (a) containing ENCDCs are injected to site(s) in the diseased (“Aganglionic”) segment of colon where newly generated enteric ganglia ((b), arrows) containing functional neurons and glia form. The transplant-derived cells integrate into the neuromuscular circuitry as confirmed with optogenetic activation (c), with the result that colonic motility is restored as demonstrated with spatiotemporal maps (d).