@article{5af8125811a94c9dad6b7480804033d1,
title = "Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity",
abstract = "The pathogenesis of ulcerative colitis (UC), a major type of inflammatory bowel disease, remains unknown. No model exists that adequately recapitulates the complexity of clinical UC. Here, we take advantage of induced pluripotent stem cells (iPSCs) to develop an induced human UC-derived organoid (iHUCO) model and compared it with the induced human normal organoid model (iHNO). Notably, iHUCOs recapitulated histological and functional features of primary colitic tissues, including the absence of acidic mucus secretion and aberrant adherens junctions in the epithelial barrier both in vitro and in vivo. We demonstrate that the CXCL8/CXCR1 axis was overexpressed in iHUCO but not in iHNO. As proof-of-principle, we show that inhibition of CXCL8 receptor by the small-molecule non-competitive inhibitor repertaxin attenuated the progression of UC phenotypes in vitro and in vivo. This patient-derived organoid model, containing both epithelial and stromal compartments, will generate new insights into the underlying pathogenesis of UC while offering opportunities to tailor interventions to the individual patient.",
author = "Sarvestani, {Samaneh K.} and Steven Signs and Bo Hu and Yunku Yeu and Hao Feng and Ying Ni and Hill, {David R.} and Fisher, {Robert C.} and Sylvain Ferrandon and DeHaan, {Reece K.} and Jennifer Stiene and Michael Cruise and Hwang, {Tae Hyun} and Xiling Shen and Spence, {Jason R.} and Huang, {Emina H.}",
note = "Funding Information: We thank the members of Huang laboratory for their help with the project, Cassandra Talerico, PhD, for her help with scientific editing, Anthony Calabro, PhD, for the generous transfer of TS-HA hydrogel technique, and Haiyan Lu, MD, as a pathologist. This project was supported by the American Society of Colorectal Surgeons Limited Project Grant 100, NIH R01 CA142808, NIH R01 CA157663, NIH U01 CA214300, and NIH R01 CA237304. We thank the Cleveland Clinic Lerner Research Institute Imaging Core, the Pluripotent Stem Cell Facility at University of Florida (Nao Terada, PhD), This work also was supported by the Cancer Tissue Engineering Collaborative (U01CA214300), the Intestinal Stem Cell Consortium (U01DK103141), a collaborative research project funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Diseases (NIAID) to J.R.S. and by the NIAID Novel, Alternative Model Systems for Enteric Diseases (NAMSED) consortium (U19AI116482) to J.R.S. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "1",
doi = "10.1038/s41467-020-20351-5",
language = "English (US)",
volume = "12",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}