A stem cell therapy for Hirschsprung Disease

Hirschsprung disease is a common disorder affecting newborn children. To save lives, the infants are operated on in the first few weeks. However, they suffer long-term complications, which we hope to prevent through stem cell replacement of missing neurons.

Hirschsprung disease (HSCR) is a congenital enteric neuropathy characterised by the lack of enteric neurons in the distal bowel, which results in a loss of propulsive motility and life-threatening constipation. Without surgical removal of the defective bowel, the infant dies. Current surgical intervention, while life-saving, frequently results in chronic, long-term complications, including constipation, faecal soiling, and associated psychosocial problems. Consequently, alternative treatments are needed.

Our studies have shown that following transplantation into the bowel, endogenous enteric neural progenitors give rise to new neurons that are electrically active, integrate into the enteric nervous system circuitry and functionally innervate the gut muscle. We have embarked on a program to rescue rats from certain death by bypassing the defective bowel, restoring function by stem cell therapy and then re-joining the bowel as illustrated below.

In this project you will participate in the rescue of Hirschsprung rats and you will evaluate recolonisation using structural and functional methods.