Neural crest neuroblasts can colonise aganglionic and ganglionic gut in vivo.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Martucciello
G
G
Scientific Institute IRCCS Policlinico San Matteo, Pavia, Italy. martucciello@yahoo.com
Brizzolara
A
A
Favre
A
A
Lombardi
L
L
Bocciardi
R
R
Sanguineti
M
M
Pini Prato
A
A
Jasonni
V
V
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D053595:Embryonic Stem Cells; D017615:Enteric Nervous System / Q000166:cytology*; D005724:Ganglia / Q000166:cytology*; D006627:Hirschsprung Disease / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D023421:Models, Animal; D009432:Neural Crest / Q000166:cytology*; D033581:Stem Cell Transplantation