A stem cell therapy for Hirschsprung Disease

• 
  Project Leader/Supervisor
  Dr Lincon Stamp, Professor John Furness

  lstamp@unimelb.edu.au; j.furness@unimelb.edu.au

  View researcher's webpage

Project Details

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, fecal soiling, and associated psychosocial problems.  Consequently, alternative treatments are needed.

In this project you will participate in our HSCR program, which includes the rescue of HSCR rats, the development of stem cell therapies and evaluation of recolonization of the enteric nervous system using structural and functional methods.

Our studies have shown that following transplantation into the bowel, exogenous enteric neural progenitors give rise to new neurons that are electrically active, integrate into the ENS 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.

Researchers

• Project supervisors: Dr Lincon Stamp, Professor John Furness
• Project members: Dr Lincon Stamp, Professor John Furness, Dr Juan Molero, Dr Cameron Adams, Ms Enie Lei

Collaborators

Dr Sebastian King (Royal Children’s Hospital)

Dr Marlene Hao

Dr Hui Yu

Dr Allan Goldstein (Mass General Hospital)

Dr Ryo Hotta (Mass General Hospital)

Research Publications

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 (2023)