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It occurs when bowel colonization by neural crest-derived enteric nervous system (ENS) precursors is incomplete during the first trimester of pregnancy. Several sources of candidate cells have been previously studied for their capacity to regenerate the ENS, including enteric neural crest stem cells (En-NCSCs) derived from native intestine or those simulated from human pluripotent stem cells (hPSCs). However, it is not yet known whether the native NCSCs other than En-NCSCs would have the potential of regenerating functional enteric neurons and producing neuron dependent motility under the intestinal environment. The present study was designed to determine whether premigratory NCSCs (pNCSCs), as a type of the nonenteric NCSCs, could form enteric neurons and mediate the motility. pNCSCs were firstly transplanted into the colon of adult mice, and were found to survive, migrate, differentiate into enteric neurons, and successfully integrate into the adult mouse colon. When the mixture of pNCSCs and human intestinal organoids was implanted into the subrenal capsule of nude mice and grown into the mature tissue-engineered intestine (TEI), the pNCSCs-derived neurons mediated neuron-dependent peristalsis of TEI. These results show that the pNCSCs that were previously assumed to not be induced by intestinal environment or cues can innervate the intestine and establish neuron-dependent motility. Future cell candidates for ENS regeneration may include nonenteric NCSCs.<\/jats:p>","DOI":"10.1002\/sctm.20-0469","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T21:46:31Z","timestamp":1611351991000},"page":"922-938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Premigratory neural crest stem cells generate enteric neurons populating the mouse colon and regulating peristalsis in tissue-engineered intestine"],"prefix":"10.1093","volume":"10","author":[{"given":"Huipu","family":"Yuan","sequence":"first","affiliation":[{"name":"Institute of Translational Medicine, and Children's Hospital Affiliated and Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People's Republic of China"},{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Hangzhou Medical College, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, and Children's Hospital Affiliated and Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People's Republic of China"},{"name":"Department of Neonatal Surgery Children's Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Mu","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, and Children's Hospital Affiliated and Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People's Republic of China"},{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Interdisciplinary Institutes of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, and Children's Hospital Affiliated and Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People's Republic of China"},{"name":"Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuelei","family":"Chen","sequence":"additional","affiliation":[{"name":"Cell Bank\/Stem Cell Bank Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Ding","sequence":"additional","affiliation":[{"name":"Cell Bank\/Stem Cell Bank Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Xi","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Department of Genetics, Division of Human Reproduction and Developmental Genetics of the Women's Hospital Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ShanShan","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Internal Neurology Children's Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical Engineering Zhejiang University, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Wang","sequence":"additional","affiliation":[{"name":"Interdisciplinary Institutes of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, School of Physical Education & Health Care East China Normal University, Shanghai, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfa","family":"Tou","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, and Children's Hospital Affiliated and Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, the Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People's Republic of China"},{"name":"Department of Neonatal Surgery Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 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