The Promise of Patient-Derived Colon Organoids to Model Ulcerative Colitis

Abstract Physiologic, molecular, and genetic findings all point to impaired intestinal epithelial function as a key element in the multifactorial pathogenesis of ulcerative colitis (UC). The lack of epithelial-directed therapies is a conspicuous weakness of our UC therapeutic armamentarium. However,...

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Veröffentlicht in:Inflammatory bowel diseases 2022-02, Vol.28 (2), p.299-308
Hauptverfasser: Ojo, Babajide A, VanDussen, Kelli L, Rosen, Michael J
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container_title Inflammatory bowel diseases
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creator Ojo, Babajide A
VanDussen, Kelli L
Rosen, Michael J
description Abstract Physiologic, molecular, and genetic findings all point to impaired intestinal epithelial function as a key element in the multifactorial pathogenesis of ulcerative colitis (UC). The lack of epithelial-directed therapies is a conspicuous weakness of our UC therapeutic armamentarium. However, a critical barrier to new drug discovery is the lack of preclinical human models of UC. Patient tissue–derived colon epithelial organoids (colonoids) are primary epithelial stem cell–derived in vitro structures capable of self-organization and self-renewal that hold great promise as a human preclinical model for UC drug development. Several single and multi-tissue systems for colonoid culture have been developed, including 3-dimensional colonoids grown in a gelatinous extracellular matrix, 2-dimensional polarized monolayers, and colonoids on a chip that model luminal and blood flow and nutrient delivery. A small number of pioneering studies suggest that colonoids derived from UC patients retain some disease-related transcriptional and epigenetic changes, but they also raise questions regarding the persistence of inflammatory transcriptional programs in culture over time. Additional research is needed to fully characterize the extent to which and under what conditions colonoids accurately model disease-associated epithelial molecular and functional aberrations. With further advancement and standardization of colonoid culture methodology, colonoids will likely become an important tool for realizing precision medicine in UC.
doi_str_mv 10.1093/ibd/izab161
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The lack of epithelial-directed therapies is a conspicuous weakness of our UC therapeutic armamentarium. However, a critical barrier to new drug discovery is the lack of preclinical human models of UC. Patient tissue–derived colon epithelial organoids (colonoids) are primary epithelial stem cell–derived in vitro structures capable of self-organization and self-renewal that hold great promise as a human preclinical model for UC drug development. Several single and multi-tissue systems for colonoid culture have been developed, including 3-dimensional colonoids grown in a gelatinous extracellular matrix, 2-dimensional polarized monolayers, and colonoids on a chip that model luminal and blood flow and nutrient delivery. A small number of pioneering studies suggest that colonoids derived from UC patients retain some disease-related transcriptional and epigenetic changes, but they also raise questions regarding the persistence of inflammatory transcriptional programs in culture over time. 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source MEDLINE; Oxford University Press Journals All Titles (1996-Current)
subjects Basic Science Review
Colitis, Ulcerative
Colon
Humans
Intestinal Mucosa
Organoids
Stem Cells
title The Promise of Patient-Derived Colon Organoids to Model Ulcerative Colitis
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