Almond S et al. (2007) Characterisation and transplantation of enteric nervous system progenitor cells. Gut 56: 489–496

Patients with Hirschsprung's disease have distal-bowel aganglionosis, caused by incomplete colonization of the embryonic gut by neural crest cells. Autologous transplantation of multipotent, self-renewing, enteric nervous system progenitor cells (ENSPCs) has been suggested as a potentially curative therapy for such patients, but work in this field is still in the preclinical stage.

Almond and colleagues have described a method that can be used to isolate ENSPCs from either embryonic mouse or postnatal human gut tissue. Briefly, mouse embryonic ceca and ganglionic bowel samples from three human patients (age range 3 weeks to 7 months) with Hirschsprung's disease, imperforate anus and colonic atresia, respectively, were dissociated and cultured. Mesenchymal cells adhered to the culture vessel and were discarded, but neural-crest-derived cells (<5% of the total) remained in suspension and proliferated to form neurospheres. These neurospheres contained neuronal and glial cells with various phenotypes, as well as multipotent ENSPCs. Mouse or human neurospheres cultured for ≥21 days could colonize explanted mouse-embryo aganglionic distal hindguts. Colonization of the entire explant with neurosphere-derived neuronal and glial cells took ∼8 days.

Although this study shows that isolating autologous ENSPCs from human ganglionic bowel soon after birth is feasible, Almond and colleagues note that future studies need to demonstrate that cultured neurospheres can colonize the postnatal bowel, a very different environment to embryonic gut. The functionality of ENSPC-derived neurons must be characterized, and the safety of their transplantation (in terms of neoplasm) needs to be assured before human trials take place.