Exposure to GDNF Enhances the Ability of Enteric Neural Progenitors to Generate an Enteric Nervous System

• Published in: Stem cell reports 2017-02, Vol.8 (2), p.476-488
• Main Authors: McKeown, Sonja J., Mohsenipour, Mitra, Bergner, Annette J., Young, Heather M., Stamp, Lincon A.
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers; Cell Count; Cell Differentiation - drug effects; Cell Movement; Cell Proliferation; Cell Size - drug effects; Cells, Cultured; Coculture Techniques; enteric nervous system; Enteric Nervous System - cytology; Enteric Nervous System - embryology; enteric neural crest; enteric neural progenitors; enteric neurospheres; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Glial Cell Line-Derived Neurotrophic Factor - pharmacology; Mice; Mice, Transgenic; migration; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neurogenesis - drug effects; Neurons - cytology; Neurons - metabolism; Phenotype; Stem Cell Transplantation; transplantation
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2016.12.013

Cell therapy is a promising approach to generate an enteric nervous system (ENS) and treat enteric neuropathies. However, for translation to the clinic, it is highly likely that enteric neural progenitors will require manipulation prior to transplantation to enhance their ability to migrate and generate an ENS. In this study, we examine the effects of exposure to several factors on the ability of ENS progenitors, grown as enteric neurospheres, to migrate and generate an ENS. Exposure to glial-cell-line-derived neurotrophic factor (GDNF) resulted in a 14-fold increase in neurosphere volume and a 12-fold increase in cell number. Following co-culture with embryonic gut or transplantation into the colon of postnatal mice in vivo, cells derived from GDNF-treated neurospheres showed a 2-fold increase in the distance migrated compared with controls. Our data show that the ability of enteric neurospheres to generate an ENS can be enhanced by exposure to appropriate factors. •Enteric neurospheres are likely to require manipulation for clinical applications•Exposure to GDNF increased the size and cell number in enteric neurospheres•GDNF-treated neurospheres showed enhanced migration after transplantation in vivo•Manipulation of enteric neurospheres can enhance the generation of enteric neurons In this article, Stamp, McKeown, and colleagues examined the effects of several candidate factors on enteric neurosphere size and behavior following transplantation in vivo. They show that exposure of enteric neurospheres to GDNF enhances their ability to generate an enteric nervous system following transplantation.