Journal
EUROPEAN JOURNAL OF PEDIATRIC SURGERY
Volume 17, Issue 1, Pages 34-40Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-2007-964952
Keywords
neural crest (NC); enteric nervous system (ENS); Hirschsprung's disease (HSCR); stem cells; animal model
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Introduction: Neural crest (NC) cells differentiate in vitro into neuroblasts, precursors of the enteric nervous system (ENS), when stimulated by specific agents. We developed a study aimed at establishing whether NC-derived neuroblasts can survive and colonise in vivo when injected into a recipient mouse gut. Materials and Methods: The neuroblast precursors of the ENS were obtained from the vagal portion of the neural tubes of 296 CD-1 and Gtrosa26 mouse embryos. The embryonic cells of Gtrosa26 mice are identifiable through beta-galactosidase activity which allows recognition by blue staining. The host used in this study was the Dom/(+) mouse, an animal model for Hirschsprung's disease (aganglionic megacolon). Dom/(+) mouse pups (n = 43) received NC-derived cells inoculated into the seromuscular layer of the gut (33/43) or directly into the peritoneal abdominal cavity (10/43). Results: All Dom/(+) mice survived the procedure and were sacrificed after 7 or 14 days. Histochemical staining detected implanted cells in all mice. These showed specific myenteric colonisation into the aganglionic and ganglionic gut. Conclusion: The striking result of this study was the specific tropism of the injected NC-derived cells to target sites under the action of unknown chemotactic agents. This experimental procedure might represent a possible treatment option for specific forms of human ENS anomaly such as total intestinal aganglionosis.
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