Neuroepithelial stem cells differentiate into neuronal phenotypes and improve intestinal motility recovery after transplantation in the aganglionic colon of the rat

The purpose of this study was to elucidate the possibility and the biological significance of intracolonic grafting of neuroepithelial stem cells (NESCs) as a therapeutic strategy for neuronal replacement in disorders of the enteric nervous system (ENS) such as aganglionosis. The enteric plexus of rat colon were eliminated by serosal application of the cationic surfactant benzalkonium chloride. NESCs were harvested from the neural tube of embryonic rat, labelled with bromodeoxyuridine (BrdU), and transplanted into the denervated colon. After 2, 4 and 8 weeks, grafted cells were visualized in colon sections by fluorescent double-staining for BrdU and neuronal, astrocytic, neurochemical or stem cell markers. Eight weeks post-transplantation, the intestinal motility was assessed by measuring the changes of intraluminal pressure responding to inflating stimulation and the responses to electrical field stimulation (EFS). Our results indicate that when transplanted into the denervated gut, NESCs survived and could differentiate into neurons and glial cells in vivo. Furthermore, inflation stimulated contraction and EFS-induced response were observed in NESCs grafted group compared with no reaction in denervated group. Therefore, NESCs can survive and function in the denervated rat colon in vivo, which indicates that NESCs provide a promising cellular replacement candidate for ENS.