title: Combination of exogenous cell transplantation and 5-HT4receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model.
abstract: Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT4receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT4receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75NTRand peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT4receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model.
authors.affiliation: Department of Pediatric Surgery, the Second Affiliated Hospital, Xi'an Jiaotong University, No 157, Xi Wu Road, Xi'an 710004, Shaanxi, China; Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi'an Jiaotong University, No 96, Yan Ta Xi Road, Xi'an 710061, Shaanxi, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Pediatric Surgery, the Second Affiliated Hospital, Xi'an Jiaotong University, No 157, Xi Wu Road, Xi'an 710004, Shaanxi, China.
authors.forename: Bai-Jun
authors.initials: BJ
authors.lastname: Zheng
authors.affiliation: Department of Pediatric Surgery, the Second Affiliated Hospital, Xi'an Jiaotong University, No 157, Xi Wu Road, Xi'an 710004, Shaanxi, China.
authors.forename: Wei-Kang
authors.initials: WK
authors.lastname: Pan
authors.affiliation: Department of Pediatric Surgery, the Second Affiliated Hospital, Xi'an Jiaotong University, No 157, Xi Wu Road, Xi'an 710004, Shaanxi, China.
authors.forename: Huai-Jie
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Pediatric Surgery, the Second Affiliated Hospital, Xi'an Jiaotong University, No 157, Xi Wu Road, Xi'an 710004, Shaanxi, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Pediatric Surgery, the Second Affiliated Hospital, Xi'an Jiaotong University, No 157, Xi Wu Road, Xi'an 710004, Shaanxi, China.
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi'an Jiaotong University, No 96, Yan Ta Xi Road, Xi'an 710061, Shaanxi, China.
authors.forename: Xin-Lin
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi'an Jiaotong University, No 96, Yan Ta Xi Road, Xi'an 710061, Shaanxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatric Surgery, the Second Affiliated Hospital, Xi'an Jiaotong University, No 157, Xi Wu Road, Xi'an 710004, Shaanxi, China. Electronic address: ygao@mail.xjtu.edu.cn.
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002478:Cells, Cultured; D006627:Hirschsprung Disease / Q000378:metabolism* / Q000473:pathology; D009025:Morpholines / Q000494:pharmacology*; D009432:Neural Crest / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D001549:Benzamides; D009025:Morpholines; D017366:Serotonin Receptor Agonists; D044422:Receptors, Serotonin, 5-HT4; C062720:mosapride
keywords: 5-HT(4) receptor agonist; Cell transplantation; Enteric nervous system; Enteric neural crest-derived cell