Abstract
Neural stem or progenitor cells have been proposed to restore gastrointestinal function in patients suffering from congenital or acquired defects of the enteric nervous system. Various, mainly embryonic cell sources have been identified for this purpose. However, immunological and ethical issues make a postnatal cell based therapy desirable. We therefore evaluated and quantified the potential of progenitor cells of the postnatal murine enteric nervous system to give rise to neurons and glial cells in vitro. Electrophysiological analysis and BrdU uptake studies provided direct evidence that generated neurons derive from expanded cells in vitro. Transplantation of isolated and expanded postnatal progenitor cells into the distal colon of adult mice demonstrated cell survival for 12 weeks (end of study). Implanted cells migrated within the gut wall and differentiated into neurons and glial cells, both of which were shown to derive from proliferated cells by BrdU uptake. This study indicates that progenitor cells isolated from the postnatal enteric nervous system might have the potential to serve as a source for a cell based therapy for neurogastrointestinal motility disorders. However, further studies are necessary to provide evidence that the generated cells are capable to positively influence the motility of the diseased gastrointestinal tract.
Highlights
The enteric nervous system (ENS) derives from vagal and sacral progenitor cells of the neural crest [1]
Neural crest stem cells enter the proximal foregut via the dorsal aorta by embryonic day 9.5 in mice
Increasing evidence has accumulated that progenitor cells originating from postnatal gut represent an adequate cell source to regenerate the ENS [16,17,18]
Summary
The enteric nervous system (ENS) derives from vagal and sacral progenitor cells of the neural crest [1]. Neural crest stem cells enter the proximal foregut via the dorsal aorta by embryonic day 9.5 in mice. Driven by a complex program of genes [2,3] the cells proliferate and migrate in a rostro-to-caudal direction in order to colonize the entire gut by embryonic day 14.5. Impairment of ENS development leads to dys- or aganglionosis of the intestine, resulting in peristaltic dysregulation, intestinal obstruction and enterocolitis as in Hirschsprung’s Disease [9,10,11]. Apart from congenital disturbances, age and disease related neurodegenerative changes of the bowel are of increasing clinical interest taking demographic developments into account [12,13,14]. Treatment strategies for age and disease related enteric neuropathies are even less defined and mainly palliative
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