Smooth muscle proteins from Hirschsprung’s disease facilitates stem cell differentiation
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Background and aims
The transplantation of neural crest derived stem cells (NCSC’s) is a potent alternative for the treatment of Hirschsprung’s disease (HSCR). Cells to be transplanted should find an appropriate microenvironment to survive and differentiate. To investigate the quality of this microenvironment, effects of HSCR-smooth-muscle-protein extracts upon NCSC’s were studied in vitro.
Postnatal human gut from children undergoing colonic resection due to HSCR was divided in segments. Smooth muscle was dissected and homogenized. Glial-cell-line-derived-neurotrophic-factor (GDNF) concentration was measured in the homogenates from the individual segment using ELISA. NCSC’s were exposed to protein extracts derived from ganglionic and aganglionic HSCR segments, and their effect upon neurite outgrowth, survival and branching was evaluated.
The amount of the factors varied considerably between the proximal and distal segments, and also from patient to patient. While extracts from proximal segments tended to have more prominent effects, all HSCR-muscle-protein extracts increased neuronal survival and network formation.
Muscle protein from aganglionic bowel supports the survival and outgrowth of NCSC’s and is so an appropriate target for neural stem cell treatment.
KeywordsNeural crest stem cells (NCSC’s) Enteric nervous system (ENS) Hirschsprung’s disease (HSCR) GDNF
We are grateful to Elvira Wink and Karin Kaiser for excellent technical support. The work was supported by the German Research Foundation (DFG SCHA 878-1 and 2).
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