title: The Contributions of Human Mini-Intestines to the Study of Intestinal Physiology and Pathophysiology.
abstract: The lack of accessibility to normal and diseased human intestine and the inability to separate the different functional compartments of the intestine even when tissue could be obtained have held back the understanding of human intestinal physiology. Clevers and his associates identified intestinal stem cells and established conditions to grow "mini-intestines" ex vivo in differentiated and undifferentiated conditions. This pioneering work has made a new model of the human intestine available and has begun making contributions to the understanding of human intestinal transport in normal physiologic conditions and the pathophysiology of intestinal diseases. However, this model is reductionist and lacks many of the complexities of normal intestine. Consequently, it is not yet possible to predict how great the advances using this model will be for understanding human physiology and pathophysiology, nor how the model will be modified to include multiple other intestinal cell types and physical forces necessary to more closely approximate normal intestine. This review describes recent studies using mini-intestines, which have readdressed previously established models of normal intestinal transport physiology and newly examined intestinal pathophysiology. The emphasis is on studies with human enteroids grown either as three-dimensional spheroids or two-dimensional monolayers. In addition, comments are provided on mouse studies in cases when human studies have not yet been described.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: mdonowit@jhmi.edu.
authors.forename: Huimin
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: mdonowit@jhmi.edu.
authors.forename: Nesrin M
authors.initials: NM
authors.lastname: Hasan
authors.affiliation: Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: mdonowit@jhmi.edu.
authors.forename: Julie G
authors.initials: JG
authors.lastname: In
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
authors.affiliation: Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: mdonowit@jhmi.edu.
authors.forename: Olga
authors.initials: O
authors.lastname: Kovbasnjuk
authors.affiliation: Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: mdonowit@jhmi.edu.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Zachos
authors.affiliation: Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: mdonowit@jhmi.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Donowitz
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D007410:Intestinal Diseases / Q000473:pathology*; D007422:Intestines / Q000473:pathology* / Q000502:physiology*; D008954:Models, Biological; D013234:Stem Cells / Q000473:pathology / Q000502:physiology
keywords: enteroids; host pathogen; intestinal physiology; organoids; transport