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Organoids and Engineered Organ Systems - 2018
Interleukin 22 Expands Transit-Amplifying Cells While Depleting Lgr5+ Stem Cells via Inhibition of Wnt and Notch Signaling
Epithelial regeneration is essential for homeostasis and repair of the mucosal barrier. In the context of infectious and immune-mediated intestinal disease, interleukin (IL) 22 is thought to augment these processes. We sought to define the mechanisms by which IL22 promotes mucosal healing.IL22 Inhibits Epithelial Stem Cell Expansion in an Ileal Organoid Model
Crohn’s disease is an inflammatory bowel disease that affects the ileum and is associated with increased cytokines. Although interleukin (IL)6, IL17, IL21, and IL22 are increased in Crohn’s disease and are associated with disrupted epithelial regeneration, little is known about their effects on the intestinal stem cells (ISCs) that mediate tissue repair. We hypothesized that ILs may target ISCs and reduce ISC-driven epithelial renewal.The Esophageal Organoid System Reveals Functional Interplay Between Notch and Cytokines in Reactive Epithelial Changes
Aberrations in the esophageal proliferation-differentiation gradient are histologic hallmarks in eosinophilic esophagitis (EoE) and gastroesophageal reflux disease. A reliable protocol to grow 3-dimensional (3D) esophageal organoids is needed to study esophageal epithelial homeostasis under physiological and pathologic conditions.Human Fetal-Derived Enterospheres Provide Insights on Intestinal Development and a Novel Model to Study Necrotizing Enterocolitis (NEC)
Untreated necrotizing enterocolitis (NEC) can lead to massive inflammation resulting in intestinal necrosis with a high mortality rate in preterm infants. Limited access to human samples and relevant experimental models have hampered progress in NEC pathogenesis. Earlier evidence has suggested that bacterial colonization of an immature and developing intestine can lead to an abnormally high inflammatory response to bacterial bioproducts. The aim of our study was to use human fetal organoids to gain insights into NEC pathogenesis.Engineered Human Gastrointestinal Cultures to Study the Microbiome and Infectious Diseases
New models to study the intestine are key to understanding intestinal diseases and developing novel treatments. Intestinal organ-like culture systems (organoids and enteroids) have substantially advanced the study of the human gastrointestinal tract. Stem cell–derived cultures produce self-organizing structures that contain the multiple differentiated intestinal epithelial cell types including enterocytes, goblet, Paneth, and enteroendocrine cells. Understanding host–microbial interactions is one area in which these cultures are expediting major advancements.Bioengineered Liver Models for Drug Testing and Cell Differentiation Studies
In vitro models of the human liver are important for the following: (1) mitigating the risk of drug-induced liver injury to human beings, (2) modeling human liver diseases, (3) elucidating the role of single and combinatorial microenvironmental cues on liver cell function, and (4) enabling cell-based therapies in the clinic. Methods to isolate and culture primary human hepatocytes (PHHs), the gold standard for building human liver models, were developed several decades ago; however, PHHs show a precipitous decline in phenotypic functions in 2-dimensional extracellular matrix–coated conventional culture formats, which does not allow chronic treatment with drugs and other stimuli.
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