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Smooth muscle proteins from Hirschsprung’s disease facilitates stem cell differentiation

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Abstract

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.

Methods

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.

Results

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.

Conclusion

Muscle protein from aganglionic bowel supports the survival and outgrowth of NCSC’s and is so an appropriate target for neural stem cell treatment.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Pediatric Surgery, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Cornelia Irene Hagl, Sabine Heumüller, Lucas Wessel & Karl-Herbert Schäfer

  2. University of Applied Sciences, Amerikastraße 1, 66482, Zweibrücken, Germany

    Markus Klotz

  3. Department of Pediatric Surgery, University of Zürich, Steinwiesstraße 75, 8032, Zurich, Switzerland

    Ulrike Subotic

  4. Department of Computer Sciences and Microsystems Technology, University of Applied Sciences, Life Science, Amerikastraße 1, 66482, Zweibrücken, Germany

    Karl-Herbert Schäfer

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  1. Cornelia Irene Hagl
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  2. Sabine Heumüller
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  4. Ulrike Subotic
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  5. Lucas Wessel
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Correspondence to Karl-Herbert Schäfer.

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Hagl, C.I., Heumüller, S., Klotz, M. et al. Smooth muscle proteins from Hirschsprung’s disease facilitates stem cell differentiation. Pediatr Surg Int 28, 135–142 (2012). https://doi.org/10.1007/s00383-011-3010-5

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