title: Characterization and transplantation of enteric neural crest cells from human induced pluripotent stem cells.
abstract: The enteric nervous system (ENS) is recognized as a second brain because of its complexity and its largely autonomic control of bowel function. Recent progress in studying the interactions between the ENS and the central nervous system (CNS) has implicated alterations of the gut/brain axis as a possible mechanism in the pathophysiology of autism spectrum disorders (ASDs), Parkinson's disease (PD) and other human CNS disorders, whereas the underlying mechanisms are largely unknown because of the lack of good model systems. Human induced pluripotent stem cells (hiPSCs) have the ability to proliferate indefinitely and differentiate into cells of all three germ layers, thus making iPSCs an ideal source of cells for disease modelling and cell therapy. Here, hiPSCs were induced to differentiate into neural crest stem cells (NCSCs) efficiently. When co-cultured with smooth muscle layers of ganglionic gut tissue, the NCSCs differentiated into different subtypes of mature enteric-like neurons expressing nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), choline acetyltransferase (ChAT) or calretinin with typical electrophysiological characteristics of functional neurons. Furthermore, when they were transplanted into aneural or aganglionic chick, mouse or human gut tissues in ovo, in vitro or in vivo, hiPSC-derived NCSCs showed extensive migration and neural differentiation capacity, generating neurons and glial cells that expressed phenotypic markers characteristic of the enteric nervous system. Our results indicate that enteric NCSCs derived from hiPSCs supply a powerful tool for studying the pathogenesis of gastrointestinal disorders and brain/gut dysfunction and represent a potentially ideal cell source for enteric neural transplantation treatments.
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China.|Guangdong Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China.
authors: W
authors: W
authors: Li
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
authors: L
authors: L
authors: Huang
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Department of Pediatric Surgery, Guangzhou Women and Children's Medical Centre, Guangzhou, China.
authors: J
authors: J
authors: Zeng
authors: Department of Blood Transfusion, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: W
authors: W
authors: Lin
authors: Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: K
authors: K
authors: Li
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
authors: J
authors: J
authors: Sun
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
authors: W
authors: W
authors: Huang
authors: Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, China.
authors: J
authors: J
authors: Chen
authors: Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, China.
authors: G
authors: G
authors: Wang
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.|Department of Cell Biology, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China.
authors: Q
authors: Q
authors: Ke
authors: Center for Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors: J
authors: J
authors: Duan
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
authors: X
authors: X
authors: Lai
authors: Center for Reproductive Medicine, Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors: R
authors: R
authors: Chen
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
authors: M
authors: M
authors: Liu
authors: Shenzhen Beike Cell Engineering Research Institute, Shenzhen, China.
authors: Y
authors: Y
authors: Liu
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China.
authors: T
authors: T
authors: Wang
authors: Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou, China.
authors: X
authors: X
authors: Yang
authors: Center for Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors: Y
authors: Y
authors: Chen
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Department of Pediatric Surgery, Guangzhou Women and Children's Medical Centre, Guangzhou, China.
authors: H
authors: H
authors: Xia
authors: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China.|Guangdong Key Laboratory of Reproductive Medicine, Guangzhou, Guangdong, China.
authors: A P
authors: AP
authors: Xiang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D018920:Coculture Techniques / Q000379:methods*; D017615:Enteric Nervous System; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D051379:Mice; D009432:Neural Crest / Q000502:physiology* / Q000637:transplantation; D058953:Neural Stem Cells / Q000502:physiology; D009474:Neurons / Q000166:cytology