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Hirschsprung’s disease: research into the biological and clinical principles of stem cell therapy

Hirschsprung’s disease is a congenital disease of the intestinal nervous system, which can lead to life-threatening bowel disorders. A new research project, which is being coordinated by the Centre for Regenerative Biology and Medicine (ZRM) in Tübingen, is paving the way for a novel cell therapy. The project is being carried out in co-operation with the NMI in Reutlingen and is being funded by a 1.1-million-euro BMBF-grant.

The human gastrointestinal tract has an autonomous nervous system with approx. 100 million neurons. This enteric nervous system, which has also been described as a “second brain” or “gut brain”, regulates the intestinal activity and influences the human immune system. Recent scientific studies undertaken by Tübingen researchers showed that the intestines of children as well as adults contain immature neural precursor cells, which can be expanded in cell culture and differentiated into functional neurons of the “gut brain”.

Immunofluorescence image of the enteric nervous system in a mouse. The red fluorescing neurons form a complex network in the intestinal wall. © Institute of Anatomy, Tübingen

These findings form the basis for the development of new cell therapies for the future treatment of enteric nervous system diseases. Hirschsprung's disease, which is named after the Danish paediatrician Harald Hirschsprung, is an innate disorder of the "gut brain" wherein particular nerve cells are absent in certain intestinal regions, particularly in the colon.

The disease affects one in 5,000 newborn babies. The disease causes disorders in the intestinal movements and hence in the transit of stool. The symptoms can range from severe constipation to life-threatening bowel obstruction and gastrointestinal perforation.

Microscopic image of green fluorescent cells of the human enteric nervous system. The nuclei of all intestinal cells fluoresce blue. © Institute of Anatomy, Tübingen

A cooperative project of the ZRM, which involves researchers from the University of Tübingen, the NMI Natural and Medical Sciences Institute in Reutlingen, the Department of Paediatric Surgery at the University Hospital in Tübingen (UKT) and the company Naturin Viscofan GmbH, is involved with the biological and clinical principles for the treatment of Hirschsprung's disease by use of stem cell therapy. In addition, these findings might provide further insights into other related neural diseases.

This project has also convinced the German Federal Ministry of Research and Education (BMBF), which has approved funding for the project under its "Cell-based regenerative medicine" programme. The funds, at around 1.1 million euro for three years, will enable the cooperation partners to obtain comprehensive research results.

At the beginning, the researchers will have to isolate neural stem and precursor cells from intestinal tissue and analyse them by using molecular biology methods in order to gain information on the cells' development and therapy potential. This part of the project will be carried out by the initiator and coordinator of the project, Dr. Lothar Just from the Institute of Anatomy at the University of Tübingen, in close co-operation with the research group that is being led by Dr. Florian Obermayr from the Department of Paediatric Surgery at the University Hospital. These researchers will also develop an animal model to test whether these cells can be successfully transplanted, and nervous tissue integrated, into the defective intestinal region.

It is necessary to analyse the cells' ion channel properties and electrical behaviour in order to assess the functionality of the cultured nerve cells. Comparative analyses will be carried out with suitable animal models and human tissue in order to discover the optimal differentiation of the electrical properties of the stem and precursor cells. Prof. Dr. Elke Guenther, an electrophysiology expert at the NMI in Reutlingen, along with her team, will carry out these important analyses.

The successful transplantation of the cells can only be achieved with suitable biocompatible carrier material. This will be supplied by the researchers' industrial partner, Naturin Viscofan GmbH, based in the city of Weinheim. The company's BioEngineering division is specialised in the production of collagen products for their use in cell biological research and medicine.

Further information:

ZRM - Centre for Regenerative Biology and Medicine
Prof. Dr. Konrad Kohler (Coordinator of the ZRM)
Paul-Ehrlich-Straße 15
72076 Tübingen                                                                                              
Tel.: +49 (0)7071 29 85030
E-mail: konrad.kohler(at)regmed.uni-tuebingen.de

Institute of Anatomy
Dr. Lothar Just (Coordinator of the BMBF-funded project) 
Österbergstrasse 3  
72074 Tübingen 
Tel.: +49 (0)7071 29 72186
E-mail: lothar.just(at)regmed.uni-tuebingen.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/hirschsprung-s-disease-research-into-the-biological-and-clinical-principles-of-stem-cell-therapy