Human enteroids as an ex-vivo model of host-pathogen interactions in the gastrointestinal tract.
Currently, 9 out of 10 experimental drugs fail in clinical studies. This has caused a 40% plunge in the number of drugs approved by the US Food and Drug Administration (FDA) since 2005. It has been suggested that the mechanistic differences between human diseases modeled in animals (mostly rodents) and the pathophysiology of human diseases might be one of the critical factors that contribute to drug failure in clinical trials. Rapid progress in the field of human stem cell technology has allowed the in-vitro recreation of human tissue that should complement and expand upon the limitations of cell and animal models currently used to study human diseases and drug toxicity. Recent success in the identification and isolation of human intestinal epithelial stem cells (Lgr5(+)) from the small intestine and colon has led to culture of functional intestinal epithelial units termed organoids or enteroids. Intestinal enteroids are comprised of all four types of normal epithelial cells and develop a crypt-villus differentiation axis. They demonstrate major intestinal physiologic functions, including Na(+) absorption and Cl(-) secretion. This review discusses the recent progress in establishing human enteroids as a model of infectious diarrheal diseases such as cholera, rotavirus, and enterohemorrhagic Escherichia coli, and use of the enteroids to determine ways to correct the diarrhea-induced ion transport abnormalities via drug therapy.
Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jennifer
J
Foulke-Abel
Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Julie
J
In
Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Olga
O
Kovbasnjuk
Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nicholas C
NC
Zachos
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Khalil
K
Ettayebi
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Sarah E
SE
Blutt
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Joseph M
JM
Hyser
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Xi-Lei
XL
Zeng
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Sue E
SE
Crawford
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
James R
JR
Broughman
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Mary K
MK
Estes
Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA mdonowit@jhmi.edu mestes@bcm.edu.
Mark
M
Donowitz
D003106:Colon; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D054884:Host-Pathogen Interactions; D006801:Humans; D007410:Intestinal Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small; D008954:Models, Biological; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D046509:Tissue Culture Techniques / Q000295:instrumentation / Q000379:methods; D023822:Tissue Engineering
Enteroids; host–pathogen interaction; intestinal pathophysiology; intestinal physiology