Stem cell therapy for the treatment of gastrointestinal motility disorders: targeting defects in neuronal wiring

The gastrointestinal (GI) tract is a complex organ that plays essential roles in the propulsion of food and waste products, nutrient and energy uptake, as well as host defense. The enteric nervous system (ENS), a meshed network of neurons and glia, controls most of these functions. During development, progenitor cells migrate down the gut and colonize the entire intestinal tube to form the ENS. However, in 1 out of 5000 live births, these progenitors do not reach the terminal end, causing the debilitating Hirschsprung’s disease, a condition in which innervation is absent from short or longer segments of large intestine. The underlying reasons are still largely unknown. Apart from this severe disorder, also subtler ENS defects can cause gut malfunction and discomfort. This is not surprising, as progenitors have the daunting task to travel long distances and bridge important junctions (esophagus to stomach, pylorus to the duodenum or distal ileum to colon). In this project we will investigate how long-distance connections in the ENS operate and study how transplanted stem cells can repair specific lesions in the mouse ENS. Last, we will use biopsies and resection specimen from Hirschsprung’s patients to study how cellular environment affects hosting transplanted induced pluripotent stem cell (iPSC) derived precursors. For each of the sections we will used advanced live imaging and specialized microscopy to monitor neuron network function and integration of transplanted cells. The exchange between both institutes guarantees exposure to both expert imaging as well as specific enteric stem cell technology.

Keywords:enteric nervous system, Hirschsprung's disease, live microscopy

Disciplines:Cell physiology, Cell therapy, Gastro-enterology, Biophotonics