Moritz Hofer, Maria A. Duque-Correa, Matthias P. Lutolf
{"title":"Patterned gastrointestinal monolayers with bilateral access as observable models of parasite gut infection","authors":"Moritz Hofer, Maria A. Duque-Correa, Matthias P. Lutolf","doi":"10.1038/s41551-024-01313-4","DOIUrl":null,"url":null,"abstract":"<p>Organoids for modelling the physiology and pathology of gastrointestinal tissues are constrained by a poorly accessible lumen. Here we report the development and applicability of bilaterally accessible organoid-derived patterned epithelial monolayers that allow the independent manipulation of their apical and basal sides. We constructed gastric, small-intestinal, caecal and colonic epithelial models that faithfully reproduced their respective tissue geometries and that exhibited stem cell regionalization and transcriptional resemblance to in vivo epithelia. The models’ enhanced observability allowed single-cell tracking and studies of the motility of cells in immersion culture and at the air–liquid interface. Models mimicking infection of the caecal epithelium by the parasite <i>Trichuris muris</i> allowed us to live image syncytial tunnel formation. The enhanced observability of bilaterally accessible organoid-derived gastrointestinal tissue will facilitate the study of the dynamics of epithelial cells and their interactions with pathogens.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"82 1","pages":""},"PeriodicalIF":26.8000,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Biomedical Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1038/s41551-024-01313-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Organoids for modelling the physiology and pathology of gastrointestinal tissues are constrained by a poorly accessible lumen. Here we report the development and applicability of bilaterally accessible organoid-derived patterned epithelial monolayers that allow the independent manipulation of their apical and basal sides. We constructed gastric, small-intestinal, caecal and colonic epithelial models that faithfully reproduced their respective tissue geometries and that exhibited stem cell regionalization and transcriptional resemblance to in vivo epithelia. The models’ enhanced observability allowed single-cell tracking and studies of the motility of cells in immersion culture and at the air–liquid interface. Models mimicking infection of the caecal epithelium by the parasite Trichuris muris allowed us to live image syncytial tunnel formation. The enhanced observability of bilaterally accessible organoid-derived gastrointestinal tissue will facilitate the study of the dynamics of epithelial cells and their interactions with pathogens.
期刊介绍:
Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.