AustralieFrV1, PubMed, Checkpoint, bibRecord, 000D31

Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.

Identifieur interne : 000D31 ( PubMed/Checkpoint ); précédent : 000D30; suivant : 000D32

Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.

Auteurs : Michael J. Workman [États-Unis] ; Maxime M. Mahe [États-Unis] ; Stephen Trisno [États-Unis] ; Holly M. Poling [États-Unis] ; Carey L. Watson [États-Unis] ; Nambirajan Sundaram [États-Unis] ; Ching-Fang Chang [États-Unis] ; Jacqueline Schiesser [États-Unis] ; Philippe Aubert [France] ; Edouard G. Stanley [Australie] ; Andrew G. Elefanty [Australie] ; Yuichiro Miyaoka [États-Unis] ; Mohammad A. Mandegar [États-Unis] ; Bruce R. Conklin [États-Unis] ; Michel Neunlist [France] ; Samantha A. Brugmann [États-Unis] ; Michael A. Helmrath [États-Unis] ; James M. Wells [États-Unis]

Source :

Nature medicine [ 1546-170X ] ; 2017.

RBID : pubmed:27869805

Descripteurs français

English descriptors

KwdEn :
- Animals, Calcium (metabolism), Cell Line, Chick Embryo, Enteric Nervous System (physiology), Enteric Nervous System (physiopathology), Gastrointestinal Motility, Hirschsprung Disease (genetics), Hirschsprung Disease (physiopathology), Homeodomain Proteins (genetics), Humans, Immunohistochemistry, In Vitro Techniques, Induced Pluripotent Stem Cells, Interstitial Cells of Cajal (physiology), Intestines (physiology), Intestines (physiopathology), Mice, Mice, SCID, Microscopy, Confocal, Models, Biological, Mutation, Myenteric Plexus (physiology), Myenteric Plexus (physiopathology), Neural Crest, Neurogenesis (physiology), Neuroglia (physiology), Neurons (physiology), Organoids, Permeability, Real-Time Polymerase Chain Reaction, Submucous Plexus (physiology), Submucous Plexus (physiopathology), Tissue Engineering (methods), Transcription Factors (genetics).
MESH :
- chemical , genetics : Homeodomain Proteins, Transcription Factors.
- chemical , metabolism : Calcium.
- genetics : Hirschsprung Disease.
- methods : Tissue Engineering.
- physiology : Enteric Nervous System, Interstitial Cells of Cajal, Intestines, Myenteric Plexus, Neurogenesis, Neuroglia, Neurons, Submucous Plexus.
- physiopathology : Enteric Nervous System, Hirschsprung Disease, Intestines, Myenteric Plexus, Submucous Plexus.
- Animals, Cell Line, Chick Embryo, Gastrointestinal Motility, Humans, Immunohistochemistry, In Vitro Techniques, Induced Pluripotent Stem Cells, Mice, Mice, SCID, Microscopy, Confocal, Models, Biological, Mutation, Neural Crest, Organoids, Permeability, Real-Time Polymerase Chain Reaction.

Abstract

The enteric nervous system (ENS) of the gastrointestinal tract controls many diverse functions, including motility and epithelial permeability. Perturbations in ENS development or function are common, yet there is no human model for studying ENS-intestinal biology and disease. We used a tissue-engineering approach with embryonic and induced pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining human-PSC-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity, as measured by rhythmic waves of calcium transients. ENS-containing HIOs grown in vivo formed neuroglial structures similar to a myenteric and submucosal plexus, had functional interstitial cells of Cajal and had an electromechanical coupling that regulated waves of propagating contraction. Finally, we used this system to investigate the cellular and molecular basis for Hirschsprung's disease caused by a mutation in the gene PHOX2B. This is, to the best of our knowledge, the first demonstration of human-PSC-derived intestinal tissue with a functional ENS and how this system can be used to study motility disorders of the human gastrointestinal tract.

DOI: 10.1038/nm.4233
PubMed: 27869805

Affiliations:

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Le document en format XML

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<author><name sortKey="Aubert, Philippe" sort="Aubert, Philippe" uniqKey="Aubert P" first="Philippe" last="Aubert">Philippe Aubert</name>
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<author><name sortKey="Stanley, Edouard G" sort="Stanley, Edouard G" uniqKey="Stanley E" first="Edouard G" last="Stanley">Edouard G. Stanley</name>
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<author><name sortKey="Elefanty, Andrew G" sort="Elefanty, Andrew G" uniqKey="Elefanty A" first="Andrew G" last="Elefanty">Andrew G. Elefanty</name>
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<author><name sortKey="Wells, James M" sort="Wells, James M" uniqKey="Wells J" first="James M" last="Wells">James M. Wells</name>
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<author><name sortKey="Sundaram, Nambirajan" sort="Sundaram, Nambirajan" uniqKey="Sundaram N" first="Nambirajan" last="Sundaram">Nambirajan Sundaram</name>
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<author><name sortKey="Chang, Ching Fang" sort="Chang, Ching Fang" uniqKey="Chang C" first="Ching-Fang" last="Chang">Ching-Fang Chang</name>
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<author><name sortKey="Aubert, Philippe" sort="Aubert, Philippe" uniqKey="Aubert P" first="Philippe" last="Aubert">Philippe Aubert</name>
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<author><name sortKey="Elefanty, Andrew G" sort="Elefanty, Andrew G" uniqKey="Elefanty A" first="Andrew G" last="Elefanty">Andrew G. Elefanty</name>
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<author><name sortKey="Miyaoka, Yuichiro" sort="Miyaoka, Yuichiro" uniqKey="Miyaoka Y" first="Yuichiro" last="Miyaoka">Yuichiro Miyaoka</name>
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<author><name sortKey="Neunlist, Michel" sort="Neunlist, Michel" uniqKey="Neunlist M" first="Michel" last="Neunlist">Michel Neunlist</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM UMR 913, University of Nantes, CHU de Nantes-Institut des Maladies de l'Appareil Digestif, Nantes</wicri:regionArea>
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<author><name sortKey="Brugmann, Samantha A" sort="Brugmann, Samantha A" uniqKey="Brugmann S" first="Samantha A" last="Brugmann">Samantha A. Brugmann</name>
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<country xml:lang="fr">États-Unis</country>
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</affiliation>
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<author><name sortKey="Helmrath, Michael A" sort="Helmrath, Michael A" uniqKey="Helmrath M" first="Michael A" last="Helmrath">Michael A. Helmrath</name>
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<country xml:lang="fr">États-Unis</country>
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<placeName><region type="state">Ohio</region>
</placeName>
</affiliation>
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<author><name sortKey="Wells, James M" sort="Wells, James M" uniqKey="Wells J" first="James M" last="Wells">James M. Wells</name>
<affiliation wicri:level="2"><nlm:affiliation>Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio</wicri:regionArea>
<placeName><region type="state">Ohio</region>
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<series><title level="j">Nature medicine</title>
<idno type="eISSN">1546-170X</idno>
<imprint><date when="2017" type="published">2017</date>
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<term>Calcium (metabolism)</term>
<term>Cell Line</term>
<term>Chick Embryo</term>
<term>Enteric Nervous System (physiology)</term>
<term>Enteric Nervous System (physiopathology)</term>
<term>Gastrointestinal Motility</term>
<term>Hirschsprung Disease (genetics)</term>
<term>Hirschsprung Disease (physiopathology)</term>
<term>Homeodomain Proteins (genetics)</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>In Vitro Techniques</term>
<term>Induced Pluripotent Stem Cells</term>
<term>Interstitial Cells of Cajal (physiology)</term>
<term>Intestines (physiology)</term>
<term>Intestines (physiopathology)</term>
<term>Mice</term>
<term>Mice, SCID</term>
<term>Microscopy, Confocal</term>
<term>Models, Biological</term>
<term>Mutation</term>
<term>Myenteric Plexus (physiology)</term>
<term>Myenteric Plexus (physiopathology)</term>
<term>Neural Crest</term>
<term>Neurogenesis (physiology)</term>
<term>Neuroglia (physiology)</term>
<term>Neurons (physiology)</term>
<term>Organoids</term>
<term>Permeability</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Submucous Plexus (physiology)</term>
<term>Submucous Plexus (physiopathology)</term>
<term>Tissue Engineering (methods)</term>
<term>Transcription Factors (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Calcium (métabolisme)</term>
<term>Cellules interstitielles de Cajal (physiologie)</term>
<term>Cellules souches pluripotentes induites</term>
<term>Crête neurale</term>
<term>Embryon de poulet</term>
<term>Facteurs de transcription (génétique)</term>
<term>Humains</term>
<term>Immunohistochimie</term>
<term>Ingénierie tissulaire ()</term>
<term>Intestins (physiologie)</term>
<term>Intestins (physiopathologie)</term>
<term>Lignée cellulaire</term>
<term>Maladie de Hirschsprung (génétique)</term>
<term>Maladie de Hirschsprung (physiopathologie)</term>
<term>Microscopie confocale</term>
<term>Modèles biologiques</term>
<term>Motilité gastrointestinale</term>
<term>Mutation</term>
<term>Neurogenèse (physiologie)</term>
<term>Neurones (physiologie)</term>
<term>Névroglie (physiologie)</term>
<term>Organoïdes</term>
<term>Perméabilité</term>
<term>Plexus myentérique (physiologie)</term>
<term>Plexus myentérique (physiopathologie)</term>
<term>Plexus nerveux sous-muqueux (physiologie)</term>
<term>Plexus nerveux sous-muqueux (physiopathologie)</term>
<term>Protéines à homéodomaine (génétique)</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Souris</term>
<term>Souris SCID</term>
<term>Système nerveux entérique (physiologie)</term>
<term>Système nerveux entérique (physiopathologie)</term>
<term>Techniques in vitro</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Homeodomain Proteins</term>
<term>Transcription Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calcium</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Hirschsprung Disease</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de transcription</term>
<term>Maladie de Hirschsprung</term>
<term>Protéines à homéodomaine</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Tissue Engineering</term>
</keywords>
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</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cellules interstitielles de Cajal</term>
<term>Intestins</term>
<term>Neurogenèse</term>
<term>Neurones</term>
<term>Névroglie</term>
<term>Plexus myentérique</term>
<term>Plexus nerveux sous-muqueux</term>
<term>Système nerveux entérique</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Enteric Nervous System</term>
<term>Interstitial Cells of Cajal</term>
<term>Intestines</term>
<term>Myenteric Plexus</term>
<term>Neurogenesis</term>
<term>Neuroglia</term>
<term>Neurons</term>
<term>Submucous Plexus</term>
</keywords>
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<term>Maladie de Hirschsprung</term>
<term>Plexus myentérique</term>
<term>Plexus nerveux sous-muqueux</term>
<term>Système nerveux entérique</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Enteric Nervous System</term>
<term>Hirschsprung Disease</term>
<term>Intestines</term>
<term>Myenteric Plexus</term>
<term>Submucous Plexus</term>
</keywords>
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<term>Cell Line</term>
<term>Chick Embryo</term>
<term>Gastrointestinal Motility</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>In Vitro Techniques</term>
<term>Induced Pluripotent Stem Cells</term>
<term>Mice</term>
<term>Mice, SCID</term>
<term>Microscopy, Confocal</term>
<term>Models, Biological</term>
<term>Mutation</term>
<term>Neural Crest</term>
<term>Organoids</term>
<term>Permeability</term>
<term>Real-Time Polymerase Chain Reaction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules souches pluripotentes induites</term>
<term>Crête neurale</term>
<term>Embryon de poulet</term>
<term>Humains</term>
<term>Immunohistochimie</term>
<term>Ingénierie tissulaire</term>
<term>Lignée cellulaire</term>
<term>Microscopie confocale</term>
<term>Modèles biologiques</term>
<term>Motilité gastrointestinale</term>
<term>Mutation</term>
<term>Organoïdes</term>
<term>Perméabilité</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Souris</term>
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<front><div type="abstract" xml:lang="en">The enteric nervous system (ENS) of the gastrointestinal tract controls many diverse functions, including motility and epithelial permeability. Perturbations in ENS development or function are common, yet there is no human model for studying ENS-intestinal biology and disease. We used a tissue-engineering approach with embryonic and induced pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining human-PSC-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity, as measured by rhythmic waves of calcium transients. ENS-containing HIOs grown in vivo formed neuroglial structures similar to a myenteric and submucosal plexus, had functional interstitial cells of Cajal and had an electromechanical coupling that regulated waves of propagating contraction. Finally, we used this system to investigate the cellular and molecular basis for Hirschsprung's disease caused by a mutation in the gene PHOX2B. This is, to the best of our knowledge, the first demonstration of human-PSC-derived intestinal tissue with a functional ENS and how this system can be used to study motility disorders of the human gastrointestinal tract.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27869805</PMID>
<DateCreated><Year>2016</Year>
<Month>11</Month>
<Day>21</Day>
</DateCreated>
<DateCompleted><Year>2017</Year>
<Month>08</Month>
<Day>14</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>08</Month>
<Day>21</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1546-170X</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>23</Volume>
<Issue>1</Issue>
<PubDate><Year>2017</Year>
<Month>Jan</Month>
</PubDate>
</JournalIssue>
<Title>Nature medicine</Title>
<ISOAbbreviation>Nat. Med.</ISOAbbreviation>
</Journal>
<ArticleTitle>Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.</ArticleTitle>
<Pagination><MedlinePgn>49-59</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/nm.4233</ELocationID>
<Abstract><AbstractText>The enteric nervous system (ENS) of the gastrointestinal tract controls many diverse functions, including motility and epithelial permeability. Perturbations in ENS development or function are common, yet there is no human model for studying ENS-intestinal biology and disease. We used a tissue-engineering approach with embryonic and induced pluripotent stem cells (PSCs) to generate human intestinal tissue containing a functional ENS. We recapitulated normal intestinal ENS development by combining human-PSC-derived neural crest cells (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial cells and showed neuronal activity, as measured by rhythmic waves of calcium transients. ENS-containing HIOs grown in vivo formed neuroglial structures similar to a myenteric and submucosal plexus, had functional interstitial cells of Cajal and had an electromechanical coupling that regulated waves of propagating contraction. Finally, we used this system to investigate the cellular and molecular basis for Hirschsprung's disease caused by a mutation in the gene PHOX2B. This is, to the best of our knowledge, the first demonstration of human-PSC-derived intestinal tissue with a functional ENS and how this system can be used to study motility disorders of the human gastrointestinal tract.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Workman</LastName>
<ForeName>Michael J</ForeName>
<Initials>MJ</Initials>
<AffiliationInfo><Affiliation>Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mahe</LastName>
<ForeName>Maxime M</ForeName>
<Initials>MM</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-2560-193X</Identifier>
<AffiliationInfo><Affiliation>Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Trisno</LastName>
<ForeName>Stephen</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Poling</LastName>
<ForeName>Holly M</ForeName>
<Initials>HM</Initials>
<AffiliationInfo><Affiliation>Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Carey L</ForeName>
<Initials>CL</Initials>
<AffiliationInfo><Affiliation>Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Nambirajan</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Ching-Fang</ForeName>
<Initials>CF</Initials>
<AffiliationInfo><Affiliation>Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Plastic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
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<ForeName>Jacqueline</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Aubert</LastName>
<ForeName>Philippe</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>INSERM UMR 913, University of Nantes, CHU de Nantes-Institut des Maladies de l'Appareil Digestif, Nantes, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Stanley</LastName>
<ForeName>Edouard G</ForeName>
<Initials>EG</Initials>
<AffiliationInfo><Affiliation>Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Elefanty</LastName>
<ForeName>Andrew G</ForeName>
<Initials>AG</Initials>
<AffiliationInfo><Affiliation>Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Pediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Miyaoka</LastName>
<ForeName>Yuichiro</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Gladstone Institutes, San Francisco, California, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mandegar</LastName>
<ForeName>Mohammad A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>Gladstone Institutes, San Francisco, California, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Conklin</LastName>
<ForeName>Bruce R</ForeName>
<Initials>BR</Initials>
<AffiliationInfo><Affiliation>Gladstone Institutes, San Francisco, California, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Departments of Medicine and Molecular and Cellular Pharmacology, University of California at San Francisco, San Francisco, California, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Neunlist</LastName>
<ForeName>Michel</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>INSERM UMR 913, University of Nantes, CHU de Nantes-Institut des Maladies de l'Appareil Digestif, Nantes, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Brugmann</LastName>
<ForeName>Samantha A</ForeName>
<Initials>SA</Initials>
<AffiliationInfo><Affiliation>Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Plastic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Helmrath</LastName>
<ForeName>Michael A</ForeName>
<Initials>MA</Initials>
<AffiliationInfo><Affiliation>Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wells</LastName>
<ForeName>James M</ForeName>
<Initials>JM</Initials>
<AffiliationInfo><Affiliation>Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>U01 DK103117</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 DK078392</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DK092456</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U18 TR000546</GrantID>
<Acronym>TR</Acronym>
<Agency>NCATS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>U18 EB021780</GrantID>
<Acronym>EB</Acronym>
<Agency>NIBIB NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>K99 DK110414</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DK098350</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
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<Month>11</Month>
<Day>21</Day>
</ArticleDate>
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<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Nat Med</MedlineTA>
<NlmUniqueID>9502015</NlmUniqueID>
<ISSNLinking>1078-8956</ISSNLinking>
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   |texte=   Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.
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	Serveur d'exploration sur les relations entre la France et l'Australie
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

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Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.

Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system.

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