Cell based therapy of Hirschsprung´s disease

• Applicant: Privatdozent Dr. Florian Michael Anton Obermayr
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 206482839

Neural stem cells and progenitor cells from the enteric nervous system (ENS) have been proposed as a cell pool for autologous cell-based therapies, providing an alternative to the unsatisfactory current treatments for enteric neuropathies such as Hirschsprung¿s (HSCR) disease. HSCR is the most common enteric neuropathy, occurring in about 1 out of 5000 live births. The primary pathology of HSCR is an absence and/or reduction of ganglion cells in the distal colon, which leads to intestinal obstruction and results in considerable morbidity and mortality. Recently, the isolation, expansion and differentiation of enteric neural stem and progenitorscells from neonatal and even from adult gut could be demonstrated. However, several important issues remain to be investigated in order to develop an autologous ENS transplantation therapy in HSCR. In this project we propose to investigate the therapeutic potential of postnatal stem and progenitor cells isolated from normal and pathological intestinal tissue of Hirschsprung's disease rats. To do this, a novel HSCR animal disease model will be developed and the capacity of progenitor cells from various cell sources to restore gastrointestinal motility will be evaluated in vivo. The integration potential of graft derived neurons will be analyzed by cell biological, molecular biological and electrophysiological methods both in vitro and in vivo. Moreover, manometric examination and colonic transit time will allow us to evaluate long-term functional impact of ENS transplantation on colonic motility.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Hosts: Professor Dr. John Furness; Professorin Heather Young, Ph.D.