Treatment of aganglionic megacolon mice via neural stem cell transplantation.

Abstract

To explore a potential methodology for treating aganglionic megacolon, neural stem cells (NSCs) expressing engineered endothelin receptor type B (EDNRB) and glial cell-derived neurotrophic factor (GDNF) genes were transplanted into the aganglionic megacolon mice. After transplantation, the regeneration of neurons in the colon tissue was observed, and expression levels of differentiation-related genes were determined. Primary culture of NSCs was obtained from the cortex of postnatal mouse brain and infected with recombinant adenovirus expressing EDNRB and GDNF genes. The mouse model of aganglionic megacolon was developed by treating the colon tissue with 0.5 % benzalkonium chloride (BAC) to selectively remove the myenteric nerve plexus that resembles the pathological changes in the human congenital megacolon. The NSCs stably expressing the EDNRB and GDNF genes were transplanted into the benzalkonium chloride-induced mouse aganglionic colon. Survival and differentiation of the implanted stem cells were assessed after transplantation. Results showed that the EDNRB and GDNF genes were able to be expressed in primary culture of NSCs by adenovirus infection. One week after implantation, grafted NSCs survived and differentiated into neurons. Compared to the controls, elevated expression of EDNRB and GDNF was determined in BAC-induced aganglionic megacolon mice with partially improved intestinal function. Those founding indicated that the genes transfected into NSCs were expressed in vivo after transplantation. Also, this study provided favorable support for the therapeutic potential of multiple gene-modified NSC transplantation to treat Hirschsprung's disease, a congenital disorder of the colon in which ganglion cells are absent.

• Authors: Xiaogang Shu, Qingliang Meng, Huijuan Jin, Jingbo Chen, Yong Xiao, Jintong Ji, Tao Qin, Guobin Wang
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 48 Issue 3 Pg. 429-37 (Dec 2013) ISSN: 1559-1182 [Electronic] United States
• PMID: 23512482 (Publication Type: Journal Article)

Chemical References

• Glial Cell Line-Derived Neurotrophic Factor
• RNA, Messenger
• Receptors, Endothelin
• Green Fluorescent Proteins

Topics

• Adenoviridae (metabolism)
• Animals
• Cell Differentiation (genetics)
• Cell Survival (genetics)
• Disease Models, Animal
• Female
• Gene Expression Regulation
• Genetic Vectors (metabolism)
• Glial Cell Line-Derived Neurotrophic Factor (genetics, metabolism)
• Green Fluorescent Proteins (metabolism)
• HEK293 Cells
• Hirschsprung Disease (genetics, pathology, therapy)
• Humans
• Male
• Mice
• Myenteric Plexus (metabolism, pathology)
• Neural Stem Cells (cytology, metabolism)
• RNA, Messenger (genetics, metabolism)
• Receptors, Endothelin (genetics, metabolism)
• Recombination, Genetic (genetics)
• Restriction Mapping
• Stem Cell Transplantation
• Transfection