Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf
{"title":"具有类似活体细胞复杂性和功能的生物工程人结肠器官组织","authors":"Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf","doi":"10.1016/j.stem.2024.05.007","DOIUrl":null,"url":null,"abstract":"<p>Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease <em>in vitro</em>. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling <em>in vivo</em> tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called “mini-colons.” By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated <em>in vivo</em>-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.</p>","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"70 1","pages":""},"PeriodicalIF":19.8000,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Bioengineered human colon organoids with in vivo-like cellular complexity and function\",\"authors\":\"Olga Mitrofanova, Mikhail Nikolaev, Quan Xu, Nicolas Broguiere, Irineja Cubela, J. Gray Camp, Michael Bscheider, Matthias P. Lutolf\",\"doi\":\"10.1016/j.stem.2024.05.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease <em>in vitro</em>. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling <em>in vivo</em> tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called “mini-colons.” By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated <em>in vivo</em>-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.</p>\",\"PeriodicalId\":9665,\"journal\":{\"name\":\"Cell stem cell\",\"volume\":\"70 1\",\"pages\":\"\"},\"PeriodicalIF\":19.8000,\"publicationDate\":\"2024-06-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell stem cell\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.stem.2024.05.007\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell stem cell","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stem.2024.05.007","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Bioengineered human colon organoids with in vivo-like cellular complexity and function
Organoids and organs-on-a-chip have emerged as powerful tools for modeling human gut physiology and disease in vitro. Although physiologically relevant, these systems often lack the environmental milieu, spatial organization, cell type diversity, and maturity necessary for mimicking human intestinal mucosa. To instead generate models closely resembling in vivo tissue, we herein integrated organoid and organ-on-a-chip technology to develop an advanced human organoid model, called “mini-colons.” By employing an asymmetric stimulation with growth factors, we greatly enhanced tissue longevity and replicated in vivo-like diversity and patterning of proliferative and differentiated cell types. Mini-colons contain abundant mucus-producing goblet cells and, signifying mini-colon maturation, single-cell RNA sequencing reveals emerging mature and functional colonocytes. This methodology is expanded to generate microtissues from the small intestine and incorporate additional microenvironmental components. Finally, our bioengineered organoids provide a precise platform to systematically study human gut physiology and pathology, and a reliable preclinical model for drug safety assessment.
期刊介绍:
Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.