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Clinical questions

Future treatment strategies for Hirschsprung Disease:
New Biomarkers, stemcell transplantation and stimulation of neuronal migration.

In Hirschsprung's disease, the switching points (ganglia) of the enteric nervous system (ENS) in the intestinal wall are missing in a variable section, starting from the rectum. Consequently the muscles in the affected section of the intestine present permanently tense and tightened which means that the passage of intestinal contents is so severely impaired that normal defecation is not possible. To date, the only treatment for this disease is surgical removal of the affected section of the intestine. Even after this surgical treatment, disturbed bowel function remains in some patients, which less often can reduce quality of life significantly. Despite Hirschsprung’s disease being surgically well manageable, according to current research less invasive forms of therapy are conceivable which makes further investigations imperative.

The disease is caused during the embryonic period, when ENS precursor cells do not multiply properly (proliferation), do not spread into the intestine (migration) or the maturation of the precursor cells into specialized cells (cell differentiation) is disturbed. Accordingly, the combination of transplantation of progenitor cells with stimulation of migration is expected to be a successful treatment option.

Therefore, we are working on therapy models for the transplantation of progenitor cells in order to examine the influence of various treatment methods on the migration of nerve cells. In order to gain a better understanding of the molecular causes of the disease and to be able to name improved diagnostic markers of Hirschsprung's disease, we analyze diseased human intestinal sections at the protein, RNA and DNA level.

Tissue Engineering of an intestinal wall– a new therapeutic approach and experimental model for Short Bowel Syndrome.

In children with short bowel syndrome, a considerable part of the bowel is no longer present due to a malformation or a bowel obstruction. Short bowel syndrome - the most common cause of chronic bowel failure - is the result. This can severely reduce the quality of life of children and, due to long-term complications, shorten the life span to childhood. The massively disturbed resorption of fluids and electrolytes and uptake of micronutrients often necessitates a parenteral nutrition via the bloodstream for years. Intestinal transplantation is associated with a high rate of transplant rejection (60% in 5-7 years) and is therefore largely abandoned.

Hence, the hope for the future lies on tissue engineering, the construction of an artificial intestinal wall in the laboratory. There is still a long way to go before clinical application will be feasible. The aim of our tissue engineering project is a better understanding of the interaction between neurons and cells of the intestinal muscle wall in an artificial tissue in order to design as natural conditions as possible. This interaction between cells is of vital importance for the remodelling of the enteric nervous system, as an adaptation process after the loss of large parts of the intestine show.

Genetic Biomarkers for Congenital Diaphragmatic Hernia:

Scientific knowledge about genetic causes of this threatening disease is poor and reliable genetic markers as predictors of severe progression are still missing.

Chromosomal abnormalities have been observed in ten percent of patients with CDH and three to ten percent of CDHs are associated with (over 70) syndromic diseases. On the other hand, the low repetition rate among siblings shows that the cause is very often due to variants that have appeared in the generation (de novo). So far more than 150 genes have been linked to CDH. Despite individual genes that are more frequently associated with CDH, no variant alone can explain more than one to two percent of CDH cases.

This suggests that the combination of different genes may in part be responsible for the development of CDH. Our challenge is to filter out the variants that are decisive for the development of the disease or to discover the interactions of genes that may explain the development of CDH.

One approach to identify new genetic variants is the examination of patients and their parents. Our pediatric surgery clinic in Mannheim holds an ideal condition for carrying out such a genetic study. Thanks to our experience with ECMO in newborns, our clinic has become the center for congenital diaphragmatic hernia to treat the most CDH patients in Europe with an average of 50 patients per year. Also, a structured follow-up program is indispensable for the early detection of secondary diseases or late complications, thus in Mannheim we examine over 200 patients with CDH every year.


Contact Person

Doctoral Thesis

For Inquiries about doctoral thesis, please contact:

Lucas Wessel

Univ.-Prof. Dr. Dr. h.c. Lucas M. Wessel

Director of the Pediatric Surgery Clinic, UMM

Research projects

For Inquiries about lab stays, master studies and research projects, please contact:

Dr. Rasul Khasanov

Resident in Pediatric Surgery
Research Fellow

Dr. María Ángeles Tapia-Laliena

Senior Scientist
Project Leader