- Bundesministerium für Bildung und Forschung (BMBF)
- Deutsches Zentrum für Luft- und Raumfahrt e.V. (DLR)
Hirschsprung's disease is characterized by the absence of certain nerve cells in the intestine or their diminution. The patients suffer from severe disturbances of the intestinal movement, which can become life-threatening. Cell therapy, based on stem and neuronal precursor cells, is intended to provide relief and compensate for the deficit of nerve cells. The functionality of cultivated and transplanted nerve cells in animal models as well as three-dimensional tissue constructs will be characterized electrophysiologically. The activity of the ion channels, which are responsible for the transmission of electrical impulses in the cell membrane of nerve cells, will be analysed.
Neural stem and progenitor cells of the enteric nervous system (ENS) are now regarded as a possible cell source for the future treatment of neurogastrointestinal diseases such as Hirschsprung's disease.
Hirschsprung's disease is the most common enteric neuropathy with an incidence of 1:5,000 and is often associated with other development-dependent anomalies. In this disease, the absence or reduction of enteric ganglion cells in the aboral colon leads to a narrowing of the affected intestinal segment and thus to an abnormal regulation of intestinal motility. More recently, the successful isolation, expansion and differentiation of human enteric neural stem and progenitor cells derived from neonatal and adult intestines has been demonstrated.
The main objective of this joint research project is to investigate the therapeutic potential of human stem and progenitor cells derived from healthy and pathologically altered material of Hirschsprung and non-Hirschsprung patients. The stem cell potential and integration capacity will be analyzed in vitro and in vivo by cell biological, molecular biological and electrophysiological methods.
The project is divided into six different subsections:
1. detailed histological characterization of cultured neural stem cells derived from healthy and hypoganglionic intestinal segments
2. evaluation of a recently discovered surface marker for the selective isolation of neural stem and progenitor cells
3. detailed electrophysiological characterization of neural cells of the enteric nervous system and of cultured neural stem cells derived from healthy and hypoganglionic intestinal segments.
4. development and production of thin biocompatible cell carriers
5. the production of three-dimensional intestinal tissue constructs for the characterization of ENS stem cells
6. evaluation of transplanted enteric stem cells and three-dimensional tissue constructs after implantation in the animal model
- Abteilung Kinderchirurgie, Universitätsklinik für Kinder und Jugendmedizin Tübingen
- Anatomisches Institut, Universität Tübingen
- Naturin GmbH & Co. KG