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.

Figure 1: Systematic approach to cell therapy for HSCR using a rate model.

Research team


  • Dr Lincon Stamp
  • Dr Juan Molero
  • Dr Cameron Adams
  • Enie Lei
  • Madeleine Di Natale


  • Stamp LA. Cell therapy for GI motility disorders: comparison of cell sources and proposed steps for treating Hirschsprung disease (2017). American Journal of Physiology: GI and Liver 312:G348-G354.
  • Stamp LA, Lei E, Liew JJ, Pustovit RV, Hao MM, Croaker DH, Furness, JB and Adams CD: Surgical method to prevent early death of neonatal rat pups with Hirschsprung disease, thus permitting development of long-term therapeutic approaches. Biology Methods and Protocols 7, bpac004 (2022).
  • Furness JB, Lei E, Hunne B, Adams CD, Burns AJ, Wykosky J, Fazio Coles TE, Fothergill LJ, Molero JC, Pustovit RV, Stamp, LA: Development of the aganglionic colon following surgical rescue in a cell therapy model of Hirschsprung disease in rat.  Disease Models & Mechanisms. 16, dmm050055.  https://doi.org/10.1242/dmm.050055

Contact us

Professor John Furness

[email protected]